The epidermal growth factor receptor ligand amphiregulin participates in the development of mouse liver fibrosis†
Open accessAbstract
UNLABELLED: The hepatic wound-healing response to chronic noxious stimuli may lead to liver fibrosis, a condition characterized by excessive deposition of extracellular matrix. Fibrogenic cells, including hepatic stellate cells and myofibroblasts, are activated in response to a variety of cytokines, growth factors, and inflammatory mediators. The involvement of members of the epidermal growth factor family in this process has been suggested. Amphiregulin (AR) is an epidermal growth factor receptor (EGFR) ligand specifically induced upon liver injury. Here, we have addressed the in vivo role of AR in experimental liver fibrosis. To this end, liver fibrosis was induced in AR+/+ and AR-/- mice by chronic CCl(4) administration. Histological and molecular markers of hepatic fibrogenesis were measured. Additionally, the response of cultured human and mouse liver fibrogenic cells to AR was evaluated. We observed that AR was expressed in isolated Kupffer cells and liver fibrogenic cells in response to inflamatory stimuli and platelet-derived growth factor, respectively. We demonstrate that the expression of alpha-smooth muscle actin and collagen deposition were markedly reduced in AR-/- mice compared to AR+/+ animals. AR-/- mice also showed reduced expression of tissue inhibitor of metalloproteinases-1 and connective tissue growth factor, two genes that responded to AR treatment in cultured fibrogenic cells. AR also stimulated cell proliferation and exerted a potent antiapoptotic effect on isolated fibrogenic cells. CONCLUSION: These results indicate that among the different EGFR ligands, AR plays a specific role in liver fibrosis. AR may contribute to the expression of fibrogenic mediators, as well as to the growth and survival of fibrogenic cells. Additionally, our data lend further support to the role of the EGFR system in hepatic fibrogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Germline deletion of Areg is protective in chronic CCl4-induced injury.
“Consistent with previous work 23 , following chronic carbon tetrachloride (CCl4 )-induced injury - a toxin-based model that leads to robust liver fibrosis and in which germline deletion of Areg is protective 29 - increased frequencies of liver Treg cells were detected (Fig. S1A).”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [29]
Chronic CCl4-induced injury leads to robust liver fibrosis.
“Consistent with previous work 23 , following chronic carbon tetrachloride (CCl4 )-induced injury - a toxin-based model that leads to robust liver fibrosis and in which germline deletion of Areg is protective 29 - increased frequencies of liver Treg cells were detected (Fig. S1A).”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [29]
Following chronic carbon tetrachloride (CCl4)-induced injury, frequencies of liver Treg cells are increased.
“Consistent with previous work 23 , following chronic carbon tetrachloride (CCl4 )-induced injury - a toxin-based model that leads to robust liver fibrosis and in which germline deletion of Areg is protective 29 - increased frequencies of liver Treg cells were detected (Fig. S1A).”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958 · see citing works
TLR4 enhances TGF-β signaling and hepatic fibrosis
Seki, E., De Minicis, S., Österreicher, C. H., Kluwe, J., Osawa, Y., Brenner, D. A., & Schwabe, R. F. (2007) · Nature Medicine · doi:10.1038/nm1663 · Cited by 1,942 · see citing works
Bataller, R. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200524282c1 · Cited by 1,480 · see citing works
ADAMs: key components in EGFR signalling and development
Blobel, C. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1548 · Cited by 1,091 · see citing works
Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ
Iredale, J. P. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30542 · Cited by 866 · see citing works
Gressner, A. M., & Weiskirchen, R. (2006) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2006.tb00292.x · Cited by 718 · see citing works
Lee, K. S., Buck, M., Houglum, K., & Chojkier, M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118304 · Cited by 537 · see citing works
Hemmann, S., Graf, J., Roderfeld, M., & Roeb, E. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.02.003 · Cited by 509 · see citing works
Fallowfield, J. A., Mizuno, M., Kendall, T. J., Constandinou, C. M., Benyon, R. C., Duffield, J. S., & Iredale, J. P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.8.5288 · Cited by 479 · see citing works
Pinzani, M., Gesualdo, L., Sabbah, G. M., & Abboud, H. E. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114363 · Cited by 477 · see citing works
Murphy, F. R., Issa, R., Zhou, X., Ratnarajah, S., Arthur, M. J. P., Benyon, C., Iredale, J. P., & Nagase, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111490200 · Cited by 432 · see citing works
The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis
Elsharkawy, A. M., Oakley, F., & Mann, D. A. (2005) · APOPTOSIS · doi:10.1007/s10495-005-1055-4 · Cited by 418 · see citing works
Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers
Cassiman, D. M., Libbrecht, L. J., Desmet, V. J., Denef, C., & Roskams, T. (2002) · Journal of Hepatology · doi:10.1016/s0168-8278(01)00260-4 · Cited by 408 · see citing works
Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach
Lautrette, A., Li, S., Alili, R., Sunnarborg, S. W., Burtin, M., Lee, D. C., Friedlander, G., & Terzi, F. (2005) · Nature Medicine · doi:10.1038/nm1275 · Cited by 342 · see citing works
Schiffer, E. R. C., Housset, C., Cacheux, W., Wendum, D., Desbois‐Mouthon, C., Rey, C., Clergue, F., Poupon, R. Y., Barbu, V. D., & Rosmorduc, O. (2005) · Hepatology · doi:10.1002/hep.20538 · Cited by 338 · see citing works
Hepatic fibrosis: molecular mechanisms and drug targets
Lotersztajn, S., Julien, B., Teixeira-Clerc, F., Grenard, P., & Mallat, A. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095906 · Cited by 325 · see citing works
Self-citationLiver extracellular matrix in health and disease
Bédossa, P., & Paradis, V. (2003) · The Journal of Pathology · doi:10.1002/path.1397 · Cited by 304 · see citing works
Reif, S. S., Lang, A., Lindquist, J. N., Yata, Y., Gäbele, E., Scanga, A. E., Brenner, D. A., & Rippe, R. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212927200 · Cited by 298 · see citing works
Yang, C., Zeisberg, M., Mosterman, B., Sudhakar, A., Yerramalla, U. L., Holthaus, K. A., Xu, L.-M., Eng, F. J., Afdhal, N. H., & Kalluri, R. (2003) · Gastroenterology · doi:10.1053/gast.2003.50012 · Cited by 282 · see citing works
Jeong, W., Park, O., Radaeva, S., & Gao, B. (2006) · Hepatology · doi:10.1002/hep.21419 · Cited by 274 · see citing works
Resistance to Carbon Tetrachloride-Induced Hepatotoxicity in Mice Which Lack CYP2E1 Expression
Wong, F. W.-Y., Chan, W. Y., & Lee, S. S. T. (1998) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1998.8547 · Cited by 251 · see citing works
Hepatic fibrosis and cirrhosis: The (myo)fibroblastic cell subpopulations involved
Guyot, C., Lepreux, S., Combe, C., Doudnikoff, É., Bioulac‐Sage, P., Balabaud, C. P., & Desmoulière, A. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.08.021 · Cited by 241 · see citing works
Bachem, M. G., Meyer, D. H., Melchior, R., Sell, K.-M., & Gressner, A. M. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115561 · Cited by 230 · see citing works
Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells
Nieto, N. (2006) · Hepatology · doi:10.1002/hep.21427 · Cited by 227 · see citing works
Cytokines and cellular crosstalk involved in the activation of fat-storing cells.
Gressner, A. M. (1995) · PubMed · Cited by 223 · see citing works
Amphiregulin: An early trigger of liver regeneration in mice
Berasain, C., García–Trevijano, E. R., Castillo, J., Erroba, E., Lee, D. C., Prìeto, J., & Avila, M. A. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.11.006 · Cited by 213 · see citing works
Self-citationSaxena, N. K., Titus, M. A., Ding, X., Floyd, J. J., Srinivasan, S., Sitaraman, S. V., & Anania, F. A. (2004) · The FASEB Journal · doi:10.1096/fj.04-1847fje · Cited by 211 · see citing works
Effects and Regulation of Connective Tissue Growth Factor on Hepatic Stellate Cells
Paradis, V., Dargère, D., Bonvoust, F., Vidaud, M., Segarini, P. R., & Bédossa, P. (2002) · Laboratory Investigation · doi:10.1097/01.lab.0000017365.18894.d3 · Cited by 189 · see citing works
Leptin Stimulates Tissue Inhibitor of Metalloproteinase-1 in Human Hepatic Stellate Cells
Cao, Q., Mak, K. M., Ren, C., & Lieber, C. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308351200 · Cited by 168 · see citing works
Novo, E., Marra, F., Zamara, E., di Bonzo, L. V., Monitillo, L., Cannito, S., Petrai, I., Mazzocca, A., Bonacchi, A., Franco, R. S. M. D., et al. (2006) · Gut · doi:10.1136/gut.2005.082701 · Cited by 167 · see citing works
Knittel, T. E., Kobold, D., Piscaglia, F., Saile, B., Neubauer, K., Mehde, M., Timpl, R., & Ramadori, G. P. (1999) · Histochemistry and Cell Biology · doi:10.1007/s004180050421 · Cited by 167 · see citing works
Svegliati‐Baroni, G., Ridolfi, F., Hannivoort, R. A., Saccomanno, S., Buist‐Homan, M., Minicis, S. D., Jansen, P. L. M., Candelaresi, C., Benedetti, A., & Moshage, H. J. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.01.007 · Cited by 162 · see citing works
Niki, T., Bleser, P. J. D., Xu, G., Berg, K. V. D., Wisse, E., & Geerts, A. E. (1996) · Hepatology · doi:10.1002/hep.510230634 · Cited by 162 · see citing works
Marra, F., Arrighi, M. C., Fazi, M., Caligiuri, A., Pinzani, M., Romanelli, R. G., Efsen, E., Laffi, G., & Geñtilini, P. (1999) · Hepatology · doi:10.1002/hep.510300406 · Cited by 160 · see citing works
Heo, J., Factor, V. M., Uren, T., Takahama, Y., Lee, J., Major, M. E., Feinstone, S. M., & Thorgeirsson, S. S. (2006) · Hepatology · doi:10.1002/hep.21441 · Cited by 146 · see citing works
Novel Role for Amphiregulin in Protection from Liver Injury
Berasain, C., García–Trevijano, E. R., Castillo, J., Erroba, E., Santamaría, M., Lee, D. C., Prìeto, J., & Avila, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413344200 · Cited by 140 · see citing works
Self-citationGeorge, J., & Tsutsumi, M. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302929 · Cited by 125 · see citing works
Molecular basis of hepatic fibrosis
Hui, A., & Friedman, S. L. (2003) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399403005684 · Cited by 115 · see citing works
Prevention of renal vascular and glomerular fibrosis by epidermal growth factor receptor inhibition
François, H., Placier, S., Flamant, M., Tharaux, P., Chansel, D., Dussaule, J., & Chatziantoniou, C. (2004) · The FASEB Journal · doi:10.1096/fj.03-0702fje · Cited by 111 · see citing works
Davaille, J., Li, L., Mallat, A., & Lotersztajn, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202798200 · Cited by 100 · see citing works
Self-citationZhou, Y., Zheng, S., Lin, J., Zhang, Q.-J., & Chen, A. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700532 · Cited by 94 · see citing works
Transforming Growth Factor-α Deficiency Reduces Pulmonary Fibrosis in Transgenic Mice
Madtes, D. K., Elston, A. L., Hackman, R. C., Dunn, A. R., & Clark, J. G. (1999) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.20.5.3526 · Cited by 82 · see citing works
Bachem, M. G., Riess, U., & Gressner, A. M. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92368-1 · Cited by 78 · see citing works
New molecular targets for hepatocellular carcinoma: the ErbB1 signaling system
Berasain, C., Castillo, J., Prìeto, J., & Avila, M. A. (2007) · Liver International · doi:10.1111/j.1478-3231.2006.01424.x · Cited by 70 · see citing works
Self-citationBachem, M. G., Meyer, D. H., Schäfer, W., Riess, U., Melchior, R., Sell, K.-M., & Gressner, A. M. (1993) · Journal of Hepatology · doi:10.1016/s0168-8278(05)80008-x · Cited by 64 · see citing works
Godichaud, S., Si‐Tayeb, K., Augè, N., Desmoulière, A., Balabaud, C. P., Payrastre, B., Nègre‐Salvayre, A., & Rosenbaum, J. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.11.001 · Cited by 26 · see citing works
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Bachem MG, Meyer D, Melchior R, Sell KM, Gressner AM. Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. J Clin Invest 1992;89:19-27.
Cited by
Sorted by citations
Emerging Functions of Amphiregulin in Orchestrating Immunity, Inflammation, and Tissue Repair
Zaiss, D. M. W., Gause, W. C., Osborne, L. C., & Artis, D. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.020 · Cited by 639 · see citing works
Immunological landscape and immunotherapy of hepatocellular carcinoma
Prìeto, J., Melero, I., & Sangro, B. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.173 · Cited by 564 · see citing works
Fibroblast-macrophage reciprocal interactions in health, fibrosis, and cancer
Buechler, M. B., Fu, W., & Turley, S. J. (2021) · Immunity · doi:10.1016/j.immuni.2021.04.021 · Cited by 494 · see citing works
Capece, D., Fischietti, M., Verzella, D., Gaggiano, A., Cicciarelli, G., Tessitore, A., Zazzeroni, F., & Alesse, E. (2012) · BioMed Research International · doi:10.1155/2013/187204 · Cited by 405 · see citing works
Berasain, C., Castillo, J., Perugorria, M. J., Latasa, M. U., Prìeto, J., & Avila, M. A. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.03704.x · Cited by 391 · see citing works
Self-citationFuchs, B. C., Hoshida, Y., Fujii, T., Wei, L., Yamada, S., Lauwers, G. Y., McGinn, C. M., DePeralta, D. K., Chen, X., Kuroda, T., et al. (2013) · Hepatology · doi:10.1002/hep.26898 · Cited by 352 · see citing works
Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease
Chen, J., Zeng, F., Forrester, S. J., Eguchi, S., Zhang, M., & Harris, R. C. (2016) · Physiological Reviews · doi:10.1152/physrev.00030.2015 · Cited by 330 · see citing works
Berasain, C., & Avila, M. A. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.01.005 · Cited by 304 · see citing works
Self-citationAllen, J. E., & Sutherland, T. E. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.06.003 · Cited by 260 · see citing works
The multiple roles of amphiregulin in human cancer
Busser, B., Sancey, L., Brambilla, E. M., Coll, J., & Hurbin, A. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2011.05.003 · Cited by 251 · see citing works
Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma
Hoshida, Y., Fuchs, B. C., Bardeesy, N. M., Baumert, T. F., & Chung, R. T. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.07.010 · Cited by 229 · see citing works
Minutti, C. M., Modak, R. V., Macdonald, F., Li, F., Smyth, D. J., Dorward, D. A., Blair, N., Husovsky, C., Muir, A., Giampazolias, E., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.008 · Cited by 228 · see citing works
EGFR Signaling in Liver Diseases
Komposch, K., & Sibilia, M. C. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms17010030 · Cited by 221 · see citing works
EGFR-activated myofibroblasts promote metastasis of pancreatic cancer
Mucciolo, G., Henríquez, J. A., Jihad, M., Teles, S. P., Manansala, J. S., Li, W., Ashworth, S., Lloyd, E. G., Cheng, P. S. W., Luo, W., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.12.002 · Cited by 215 · see citing works
Jiao, J., Friedman, S. L., & Aloman, C. (2009) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3283279668 · Cited by 203 · see citing works
Fujii, T., Fuchs, B. C., Yamada, S., Lauwers, G. Y., Kulu, Y., Goodwin, J. M., Lanuti, M. D., & Tanabe, K. K. (2010) · BMC Gastroenterology · doi:10.1186/1471-230x-10-79 · Cited by 202 · see citing works
Venkataraman, T., & Frieman, M. B. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.03.022 · Cited by 193 · see citing works
Quercetin Treatment Ameliorates Inflammation and Fibrosis in Mice with Nonalcoholic Steatohepatitis3
Marcolin, É., San‐Miguel, B., Vallejo, D., Tieppo, J., Marroni, N. P., González‐Gallego, J., & Tuñón, M. J. (2012) · Journal of Nutrition · doi:10.3945/jn.112.165274 · Cited by 177 · see citing works
Role of Epidermal Growth Factor Receptor (EGFR) and Its Ligands in Kidney Inflammation and Damage
Rayego‐Mateos, S., Rodrigues-Díez, R. R., Morgado‐Pascual, J. L., Valentijn, F. A., Valdivielso, J. M., Goldschmeding, R., & Ruiz-Ortega, M. (2018) · Mediators of Inflammation · doi:10.1155/2018/8739473 · Cited by 177 · see citing works
The EGFR signalling system in the liver: from hepatoprotection to hepatocarcinogenesis
Berasain, C., & Avila, M. A. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-013-0907-x · Cited by 175 · see citing works
Self-citationZhou, Y., Lee, J., Lee, C.-M., Cho, W., Kang, M., Koff, J. L., Yoon, P.-O., Chae, J., Park, H.-O., Elias, J. A., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.356824 · Cited by 143 · see citing works
Jäger, B., Schupp, J. C., Plappert, L., Terwolbeck, O., Artysh, N., Kayser, G., Engelhard, P., Adams, T. S., Zweigerdt, R., Kempf, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33193-0 · Cited by 142 · see citing works
Regulation of hepatic stellate cells by connective tissue growth factor
Huang, G. (2012) · Frontiers in bioscience · doi:10.2741/4067 · Cited by 135 · see citing works
Machado, M. V., Michelotti, G. A., Pereira, T. A., Xie, G., Premont, R., Cortez-Pinto, H., & Diehl, A. M. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.05.031 · Cited by 135 · see citing works
The Epidermal Growth Factor Receptor: A Link Between Inflammation and Liver Cancer
Berasain, C., Perugorria, M. J., Latasa, M. U., Castillo, J., Goñi, S., Santamaría, M., Prìeto, J., & Avila, M. A. (2009) · Experimental Biology and Medicine · doi:10.3181/0901-mr-12 · Cited by 132 · see citing works
Self-citationChettouh, H., Fartoux, L., Aoudjehane, L., Wendum, D., Clapéron, A., Chrétien, Y., Rey, C., Scatton, O., Soubrane, O., Conti, F., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3824 · Cited by 131 · see citing works
ADAM17 substrate release in proximal tubule drives kidney fibrosis
Kefaloyianni, E., Muthu, M. L., Kaeppler, J., Sun, X., Sabbisetti, V. S., Chalaris, A., Rose‐John, S., Wong, E., Sagi, I., Waikar, S. S., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.87023 · Cited by 128 · see citing works
Urtasun, R., Latasa, M. U., Demartis, M. I., Balzani, S., Goñi, S., García‐Irigoyen, O., Elizalde, M., Azcona, M., Pascale, R. M., Feo, F., et al. (2010) · Hepatology · doi:10.1002/hep.24587 · Cited by 117 · see citing works
Self-citationSavage, T. M., Fortson, K. T., de los Santos-Alexis, K., Oliveras-Alsina, A., Rouanne, M., Rae, S. S., Gamarra, J. R., Shayya, H., Kornberg, A., Cavero, R., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.009 · Cited by 115 · see citing works
Venkataraman, T., Coleman, C. M., & Frieman, M. B. (2017) · Journal of Virology · doi:10.1128/jvi.00182-17 · Cited by 113 · see citing works
Sobrevals, L., Rodríguez‐Ortigosa, C. M., Romero-Trevejo, J. L., Gondi, G., Monreal‐Santesteban, I., Pañeda, A., Juanarena, N., Arcelus, S., Razquin, N., Guembe, L., et al. (2009) · Hepatology · doi:10.1002/hep.23412 · Cited by 98 · see citing works
Hu, Y., Xuefeng, Y., Shandong, W., & Jianhua, X. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.03.024 · Cited by 97 · see citing works
Airway Basal Cells, Protectors of Epithelial Walls in Health and Respiratory Diseases
Ruysseveldt, E., Martens, K., & Steelant, B. (2021) · Frontiers in Allergy · doi:10.3389/falgy.2021.787128 · Cited by 96 · see citing works
Targeting senescent cells improves functional recovery after spinal cord injury
Paramos-de-Carvalho, D., Martins, I., Cristóvão, A. M., Dias, A. F., Neves-Silva, D., Pereira, T., Chapela, D., Farinho, A., Jacinto, A., & Saúde, L. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109334 · Cited by 74 · see citing works
Animal models for the study of liver fibrosis: new insights from knockout mouse models
Hayashi, H., & Sakai, T. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00013.2011 · Cited by 73 · see citing works
EGFR Signaling in Lung Fibrosis
Schramm, F., Schaefer, L., & Wygrecka, M. (2022) · Cells · doi:10.3390/cells11060986 · Cited by 71 · see citing works
Xu, Y., Chen, M., Liu, G., Yang, D., Fu, L., Zhang, M., Zhang, Z., Xia, H., Yao, S., & Zhang, S. (2016) · Anesthesiology · doi:10.1097/aln.0000000000001026 · Cited by 71 · see citing works
Bone Marrow CD11c+ Cell–Derived Amphiregulin Promotes Pulmonary Fibrosis
Ding, L., Liu, T., Wu, Z. B., Hu, B., Nakashima, T., Ullenbruch, M. R., Santos, F. G. D. L., & Phan, S. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502479 · Cited by 70 · see citing works
Cheng, W.-H., Kao, S.-Y., Chen, C., Yuliani, F. S., Lin, L., Lin, C., & Chen, B.-C. (2022) · Respiratory Research · doi:10.1186/s12931-022-02285-2 · Cited by 68 · see citing works
Santamaría, E., Rodríguez‐Ortigosa, C. M., Uriarte, I., Latasa, M. U., Urtasun, R., Álvarez‐Sola, G., Bárcena‐Varela, M., Colyn, L., Arcelus, S., Jiménez, M., et al. (2018) · Hepatology · doi:10.1002/hep.30348 · Cited by 66 · see citing works
Self-citationThe Role of ARF6 in Biliary Atresia
Ningappa, M., So, J., Glessner, J., Ashokkumar, C., Ranganathan, S., Min, J., Higgs, B. W., Sun, Q., Haberman, K., Schmitt, L. A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138381 · Cited by 65 · see citing works
Bhushan, B., & Michalopoulos, G. K. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109090 · Cited by 66 · see citing works
Kefaloyianni, E., Raja, M. R. K., Schumacher, J., Muthu, M. L., Krishnadoss, V., Waikar, S. S., & Herrlich, A. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019030321 · Cited by 63 · see citing works
Relationships Among Stellate Cell Activation, Progenitor Cells, and Hepatic Regeneration
Roskams, T. (2008) · Clinics in Liver Disease · doi:10.1016/j.cld.2008.07.014 · Cited by 60 · see citing works
Identification of regenerative roadblocks via repeat deployment of limb regeneration in axolotls
Bryant, D. M., Sousounis, K., Payzin‐Dogru, D., Bryant, S., Sandoval, A. G. W., Fernandez, J. M., Mariano, R., Oshiro, R., Wong, A. Y. L., Leigh, N. D., et al. (2017) · npj Regenerative Medicine · doi:10.1038/s41536-017-0034-z · Cited by 59 · see citing works
García‐Irigoyen, O., Carotti, S., Latasa, M. U., Uriarte, I., Fernández‐Barrena, M. G., Elizalde, M., Urtasun, R., Gentilucci, U. V., Morini, S., Bañales, J. M., et al. (2013) · Liver International · doi:10.1111/liv.12337 · Cited by 56 · see citing works
Self-citationEpidermal growth factor receptor activation is essential for kidney fibrosis development
Cao, S., Pan, Y., Terker, A. S., Arroyo, J. P., Wang, Y., Tang, J., Niu, A., Kar, S. A., Jiang, M., Luo, W., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43226-x · Cited by 57 · see citing works
McKee, C. M., Sigala, B., Soeda, J., Mouralidarane, A., Morgan, M. L., Mazzoccoli, G., Rappa, F., Cappello, F., Cabibi, D., Pazienza, V., et al. (2015) · Scientific Reports · doi:10.1038/srep08812 · Cited by 54 · see citing works
Latasa, M. U., Salis, F., Urtasun, R., García‐Irigoyen, O., Elizalde, M., Uriarte, I., Santamaría, M., Feo, F., Pascale, R. M., Prìeto, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052711 · Cited by 54 · see citing works
Self-citationSingh, S. S., Chauhan, S. B., Kumar, A., Kumar, S. B., Engwerda, C. R., Sundar, S., & Kumar, R. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30615 · Cited by 53 · see citing works
Impairment of pre-mRNA splicing in liver disease: Mechanisms and consequences
Berasain, C. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i25.3091 · Cited by 53 · see citing works
Self-citationCrespo, I., San‐Miguel, B., Fernández, A. M. C., de Urbina, J. J. O., González‐Gallego, J., & Tuñón, M. J. (2014) · Translational research · doi:10.1016/j.trsl.2014.10.003 · Cited by 53 · see citing works
Production of amphiregulin and recovery from influenza is greater in males than females
Vermillion, M. S., Ursin, R. L., Kuok, D. I. T., Steeg, L. G. V., Wohlgemuth, N., Hall, O. J., Fink, A. L., Sasse, E., Nelson, A., Ndeh, R., et al. (2018) · Biology of Sex Differences · doi:10.1186/s13293-018-0184-8 · Cited by 53 · see citing works
Liu, L., Jin, X., Hu, C., Zhang, Y., Zhou, Z., Li, R., & Shen, C. (2018) · Basic Research in Cardiology · doi:10.1007/s00395-018-0669-y · Cited by 52 · see citing works
RetractedSustained amphiregulin expression in intermediate alveolar stem cells drives progressive fibrosis
Zhao, R., Wang, Z., Wang, G., Geng, J., Wu, H., Liu, X., Bin, E., Sui, J., Dai, H., & Tang, N. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.07.004 · Cited by 51 · see citing works
Altered circadian rhythm of the clock genes in fibrotic livers induced by carbon tetrachloride
Chen, P., Kakan, X., & Zhang, J. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.03.019 · Cited by 43 · see citing works
Cuevas, M. J., Tieppo, J., Marroni, N. P., Tuñón, M. J., & González‐Gallego, J. (2011) · Journal of Nutrition · doi:10.3945/jn.111.140954 · Cited by 42 · see citing works
Loss of clock gene mPer2 promotes liver fibrosis induced by carbon tetrachloride
Chen, P., Han, Z., Yang, P., Zhu, L., Hua, Z., & Zhang, J. (2010) · Hepatology Research · doi:10.1111/j.1872-034x.2010.00695.x · Cited by 41 · see citing works
Son, S. S., Hwang, S., Park, J. H., Ko, Y., Yun, S., Lee, J., Son, B., Kim, T. R., Park, H.-O., & Lee, E. Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-81726-2 · Cited by 39 · see citing works
Huang, G., Besner, G. E., & Brigstock, D. R. (2012) · Laboratory Investigation · doi:10.1038/labinvest.2012.3 · Cited by 37 · see citing works
Heo, Y. J., Lee, N., Choi, S., Jeon, J. Y., Han, S. J., Kim, D. J., KANG, Y. Y., Lee, K. W., & Kim, H. J. (2023) · Mediators of Inflammation · doi:10.1155/2023/2364121 · Cited by 34 · see citing works
Regulatory role and translational potential of CCL11 in liver fibrosis
Kong, M., Dong, W., Kang, A., Kuai, Y., Xu, T., Fan, Z., Shi, L., Sun, D., Lu, Y., Li, Z., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000287 · Cited by 34 · see citing works
Hepatocyte ERBB3 and EGFR are required for maximal CCl 4 -induced liver fibrosis
Scheving, L. A., Zhang, X., Threadgill, D. W., & Russell, W. E. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00423.2015 · Cited by 33 · see citing works
Parra, L. M., Hartmann, M., Schubach, S., Li, Y., Herrlich, P. A., & Herrlich, A. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00500-15 · Cited by 32 · see citing works
Benkheil, M., Paeshuyse, J., Neyts, J. H., Haele, M. V., Roskams, T., & Liekens, S. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.07.011 · Cited by 32 · see citing works
Pei, R., Chen, H., Lu, L., Zhu, W., Beckebaum, S., Cicinnati, V. R., Lu, M., & Chen, X. (2011) · Journal of General Virology · doi:10.1099/vir.0.032581-0 · Cited by 31 · see citing works
Signal molecule-mediated hepatic cell communicationduring liver regeneration
Zheng, Z., Weng, S., & Yu, Y. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.5776 · Cited by 31 · see citing works
Todd, J. L., Kelly, F. L., Nagler, A. E., Banner, K., Pavlisko, E. N., Belperio, J. A., Brass, D. M., Weigt, S. S., & Palmer, S. M. (2019) · American Journal of Transplantation · doi:10.1111/ajt.15667 · Cited by 29 · see citing works
Amphiregulin Aggravates Glomerulonephritis via Recruitment and Activation of Myeloid Cells
Melderis, S., Hagenstein, J., Warkotsch, M. T., Dang, J., Herrnstadt, G. R., Niehus, C. B., Neumann, K., Panzer, U., Berasain, C., Avila, M. A., et al. (2020) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019111215 · Cited by 29 · see citing works
Self-citationMacrophages in the pancreas: Villains by circumstances, not necessarily by actions
Cruz, A. F., Rohban, R., & Esni, F. (2020) · Immunity, Inflammation and Disease · doi:10.1002/iid3.345 · Cited by 28 · see citing works
Wu, X., Dong, W., Zhang, T., Ren, H., Wang, J., Shang, L., Zhu, Z., Zhu, W., Shi, X., & Xu, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.591246 · Cited by 29 · see citing works
Latasa, M. U., Gil, C., Fernández‐Barrena, M. G., Rodríguez‐Ortigosa, C. M., Bañales, J. M., Urtasun, R., Goñi, S., Méndez, M., Arcelus, S., Juanarena, N., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015690 · Cited by 29 · see citing works
Self-citationTryndyak, V., de Conti, A., Doerge, D. R., Olson, G. R., Beland, F. A., & Pogribny, I. P. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1786-8 · Cited by 29 · see citing works
Li, X., Li, M., Deng, S., Tian, Y. P., Ma, Y., Yang, H., Zhang, J., Zheng, Y., & Ma, L. (2021) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115992 · Cited by 27 · see citing works
The Roles of Kidney-Resident ILC2 in Renal Inflammation and Fibrosis
Nagashima, R., & Iyoda, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.688647 · Cited by 27 · see citing works
Procollagen C-Proteinase Enhancer 1 (PCPE-1) as a Plasma Marker of Muscle and Liver Fibrosis in Mice
Hassoun, E., Safrin, M., Ziv, H., Pri‐Chen, S., & Kessler, E. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159606 · Cited by 27 · see citing works
Regulation of Fibrotic Processes in the Liver by ADAM Proteases
Schmidt‐Arras, D., & Rose‐John, S. (2019) · Cells · doi:10.3390/cells8101226 · Cited by 27 · see citing works
Meirelles, L. D. S., Marson, R. F., Solari, M. I. G., & Nardi, N. B. (2020) · Cells · doi:10.3390/cells9010188 · Cited by 26 · see citing works
Ji, M., Liu, Y., Zuo, Z., Xu, C., Lin, L., & Li, Y. (2022) · Biology Direct · doi:10.1186/s13062-022-00334-w · Cited by 26 · see citing works
Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection
Shen, C., Wang, S., Wang, S., Lin, S., Wu, J., Lin, C.-T., & Liu, Y. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5482 · Cited by 24 · see citing works
Oikawa, H., Maesawa, C., Tatemichi, Y., Nishinari, Y., Nishiya, M., Mizugai, H., Ikeda, A., Oikawa, K., Takikawa, Y., & Masuda, T. (2014) · Life Sciences · doi:10.1016/j.lfs.2013.12.028 · Cited by 23 · see citing works
Jiang, Y., Xie, Y., Peng, C.-W., Yao, K., Xue-ying, L., Zhan, S., Zhuang, H., Huang, H.-T., Liu, X.-H., Huang, X., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.865097 · Cited by 22 · see citing works
Nakanishi, T., Koma, Y., Miyako, S., Torigoe, R., Yokoo, H., Omori, M., Yamanaka, K., Ishihara, N., Tsukamoto, S., Kodama, T., et al. (2024) · Cells · doi:10.3390/cells13201733 · Cited by 22 · see citing works
Pardo–Saganta, A., Latasa, M. U., Castillo, J., Alvarez–Asiain, L., Perugorria, M. J., Sarobe, P., Rodríguez‐Ortigosa, C. M., Prìeto, J., Berasain, C., Santamaría, M., et al. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.06.030 · Cited by 22 · see citing works
Self-citationDahlhoff, M., Schäfer, M., Wolf, E., & Schneider, M. R. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.11.001 · Cited by 22 · see citing works
Metalloproteinases in liver fibrosis: current insights
Zbodakova, O., Chalupský, K., Turečková, J., & Sedláček, R. (2017) · Metalloproteinases In Medicine · doi:10.2147/mnm.s124363 · Cited by 22 · see citing works
The ST2+ Treg/amphiregulin axis protects from immune-mediated hepatitis
Wachtendorf, S., Jonin, F., Ochel, A., Heinrich, F., Westendorf, A. M., Tiegs, G., & Neumann, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1351405 · Cited by 21 · see citing works
New and Old Key Players in Liver Cancer
Cuesta, Á. M., Palao, N., Bragado, P., Gutiérrez-Uzquiza, Á., Herrera, B. M., Sánchez, A., & Porrás, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417152 · Cited by 22 · see citing works
ILC2s in infectious diseases and organ-specific fibrosis
Kindermann, M., Knipfer, L., Atreya, I., & Wirtz, S. J. (2018) · Seminars in Immunopathology · doi:10.1007/s00281-018-0677-x · Cited by 21 · see citing works
Yao, H., Zhu, Y., Lu, H., Ju, H., Xu, S., Qiao, Y., & Wei, S.-J. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110672 · Cited by 20 · see citing works
Liu, L., Song, S., Zhang, Y. P., Wang, D., Zhou, Z., Chen, Y., Jin, X., Hu, C. F., & Shen, C. X. (2020) · Experimental Cell Research · doi:10.1016/j.yexcr.2020.111950 · Cited by 20 · see citing works
RetractedKwon, S. H., Jeong, S. W., Jang, J. Y., Lee, J. E., Lee, S. H., Kim, S. G., Kim, Y. S., Cho, Y. D., Kim, H. S., Kim, B. S., et al. (2012) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2012.18.3.287 · Cited by 18 · see citing works
Cheng, Y., Liu, P., Hou, T., Maimaitisidike, M., Ababaikeli, R., & Abudureyimu, A. (2018) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-018-3013-3 · Cited by 18 · see citing works
Type 2 Innate Lymphoid Cells in Liver and Gut: From Current Knowledge to Future Perspectives
Ochel, A., Tiegs, G., & Neumann, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081896 · Cited by 18 · see citing works
Amphiregulin as a driver of tissue fibrosis
Zaiss, D. M. W. (2019) · American Journal of Transplantation · doi:10.1111/ajt.15743 · Cited by 18 · see citing works
Liu, Z., Su, Q.-Q., Wang, Y., Wu, X., & Lv, X. (2022) · Drug Design Development and Therapy · doi:10.2147/dddt.s346376 · Cited by 17 · see citing works
Awad, A. E., Ebrahim, M., Eissa, L. A., & El‐Shishtawy, M. M. (2019) · International Journal of Hematology-Oncology and Stem Cell Research · doi:10.18502/ijhoscr.v13i3.1275 · Cited by 16 · see citing works
Gao, Q., Wu, Z., Jinge, Y., Miao, Y., Zuoguan, C., Diao, Y., Jinfeng, Y., Jia, J., Yijia, G., Wei-min, L., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.761300 · Cited by 16 · see citing works
Tuleta, I., & Frangogiannis, N. G. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00403.2025 · Cited by 15 · see citing works
Wang, X., Deng, B., Yu, M., Zeng, T., Chen, Y., Hu, J., Wu, Q., & Li, A. (2021) · Biomaterials Science · doi:10.1039/d1bm01246k · Cited by 15 · see citing works
- Authors
- Perugorria, M. J., Latasa, M. U., Nicou, A., Cartagena‐Lirola, H., Castillo, J., Goñi, S., Vespasiani‐Gentilucci, U., Zagami, M. G., Lotersztajn, S., Prieto, J., Berasain, C., & Avila, M. A.
- Affiliations
- Centro de Investigación Médica Aplicada (ES)
- Università Campus Bio-Medico (IT)
- Inserm (FR)
- Corresponding author
- Berasain, Carmen
- Avila, Matias A.
- ORCID
- Venue
- Hepatology
- Published
- 2008-10
- Volume
- 48
- Issue
- 4
- Pages
- 1251-1261
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2086933932
- Cited by
- 151
- References
- 47
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 12 · 2023: 10 · 2022: 8 · 2021: 13 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Gobierno de Navarra
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- amphiregulin, liver fibrosis, epidermal growth factor receptor, hepatic stellate cells, myofibroblasts, Kupffer cells, carbon tetrachloride-induced liver injury, alpha-smooth muscle actin, collagen deposition, TIMP-1, connective tissue growth factor, anti-apoptotic effects, cell proliferation, platelet-derived growth factor, extracellular matrix deposition
- MeSH terms
- Animals, Carbon Tetrachloride, Cell Line, Cells, Cultured, Disease Models, Animal, Extracellular Matrix, Glycoproteins, Humans, Ligands, Liver, Liver Cirrhosis, Male, Signal Transduction, Apoptosis, Mice, Knockout, Hepatocytes, Intercellular Signaling Peptides and Proteins, Mice, ErbB Receptors, EGF Family of Proteins, Amphiregulin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
