LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice
Abstract
Although it is clear that bile acid accumulation is the major initiator of fibrosis caused by cholestatic liver disease, endotoxemia is a common side effect. However, the depletion of hepatic macrophages with gadolinium chloride blunts hepatic fibrosis. Because endotoxin is a key activator of hepatic macrophages, this study was designed to test the hypothesis that LPS signaling through CD14 contributes to hepatic fibrosis caused by experimental cholestasis. Wild-type mice and CD14 knockout mice (CD14 −/− ) underwent sham operation or bile duct ligation and were killed 3 wk later. Measures of liver injury, such as focal necrosis, biliary cell proliferation, and inflammatory cell influx, were not significantly different among the strains 3 wk after bile duct ligation. Markers of liver fibrosis such as Sirius red staining, liver hydroxyproline, and α-smooth muscle actin expression were blunted in CD14 −/− mice compared with wild-type mice after bile duct ligation. Despite no difference in lymphocyte infiltration, the macrophage/monocyte activation marker OX42 (CD11b) and the oxidative stress/lipid peroxidation marker 4-hydroxynonenal were significantly upregulated in wild-type mice after bile duct ligation but not in CD14 −/− mice. Increased profibrogenic cytokine mRNA expression in the liver after bile duct ligation was significantly blunted in CD14 −/− mice compared with the wild type. The hypothesis that LPS was involved in experimental cholestatic liver fibrosis was tested using mice deficient in LPS-binding protein (LBP −/− ). LBP −/− mice had less liver injury and fibrosis (Siruis red staining and hydroxyproline content) compared with wild-type mice after bile duct ligation. In conclusion, these data demonstrate that endotoxin in a CD14-dependent manner exacerbates hepatic fibrogenesis and macrophage activation to produce oxidants and cytokines after bile duct ligation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
TLR4, CD14 and lipopolysaccharide-binding protein have key roles in experimental toxic and cholestatic liver fibrosis.
“Studies in knockout mice have highlighted a key role for TLR4 and other important mediators in the TLR4 signalling pathway, such as CD14 and lipopolysaccharide-binding protein (LBP), in experimental models of toxic and cholestatic liver fibrosis73,74.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [74]
Cites
Paik, Y.-H., Schwabe, R. F., Bataller, R., Russo, M. P., Jobin, C., & Brenner, D. A. (2003) · Hepatology · doi:10.1053/jhep.2003.50182 · Cited by 651 · see citing works
Kupffer Cell Engulfment of Apoptotic Bodies Stimulates Death Ligand and Cytokine Expression
Canbay, A. E., Feldstein, A. E., Higuchi, H., Werneburg, N., Grambihler, A., Bronk, S. F., & Gores, G. J. (2003) · Hepatology · doi:10.1053/jhep.2003.50472 · Cited by 469 · see citing works
Bissell, D. M., Wang, S. S., Jarnagin, W. R., & Roll, F. J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118055 · Cited by 419 · see citing works
Fas enhances fibrogenesis in the bile duct ligated mouse: A link between apoptosis and fibrosis
Canbay, A. E., Higuchi, H., Bronk, S. F., Taniai, M., Sebo, T. J., & Gores, G. J. (2002) · Gastroenterology · doi:10.1053/gast.2002.35953 · Cited by 300 · see citing works
Selective Retention of Activated CD8+ T Cells by the Normal Liver
Mehal, W. Z., Juedes, A. E., & Crispe, I. N. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.6.3202 · Cited by 253 · see citing works
Hepatic injury induced by bile salts: Correlation between biochemical and morphological events
Schmucker, D. L., Ohta, M., Kanai, S., Sato, Y., & Kitani, K. (1990) · Hepatology · doi:10.1002/hep.1840120523 · Cited by 207 · see citing works
Guebre‐Xabier, M., Yang, S., Lin, H. Z., Schwenk, R., Krzych, U., & Diehl, A. M. (2000) · Hepatology · doi:10.1002/hep.510310313 · Cited by 192 · see citing works
Gujral, J. S., Liu, J., Farhood, A. I., Hinson, J., & Jaeschke, H. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00318.2003 · Cited by 167 · see citing works
Rivera, C. A., Bradford, B. U., Hunt, K. J., Adachi, Y., Schrum, L. W., Koop, D. R., Burchardt, E.-R., Rippe, R. A., & Thurman, R. G. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.1.g200 · Cited by 165 · see citing works
Self-citationBenedetti, A., Alvaro, D., Bassotti, C., Gigliozzi, A., Ferretti, G., Rosa, T. L., Sario, A. D., Baiocchi, L., & Jézéquel, A. M. (1997) · Hepatology · doi:10.1002/hep.510260102 · Cited by 106 · see citing works
Mehal, W., Azzaroli, F., & Crispe, I. (2001) · Journal of Immunology · doi:10.4049/jimmunol.167.2.667 · Cited by 103 · see citing works
Liu, Z., Sakamoto, T., Ezure, T., Yokomuro, S., Murase, N., Michalopoulos, G. K., & Demetris, A. J. (1998) · Hepatology · doi:10.1002/hep.510280514 · Cited by 103 · see citing works
Kupffer cells are responsible for liver cirrhosis induced by carbon tetrachloride
Muriel, P., & Escobar, Y. (2003) · Journal of Applied Toxicology · doi:10.1002/jat.892 · Cited by 103 · see citing works
Zhong, Z., Froh, M., Wheeler, M., Smutney, O. M., Lehmann, T., & Thurman, R. (2002) · Gene Therapy · doi:10.1038/sj.gt.3301638 · Cited by 67 · see citing works
Self-citationObstructive jaundice promotes bacterial translocation in humans.
Ma, K., It, K., Çöl, C., Tekelı, A., Tanık, A., & Köksoy, C. (1999) · PubMed · Cited by 67 · see citing works
Endotoxemia in human obstructive jaundice
Ingoldby, C. J. H., McPherson, G. A. D., & Blumgart, L. H. (1984) · The American Journal of Surgery · doi:10.1016/0002-9610(84)90197-1 · Cited by 49 · see citing works
Infiltrating neutrophils in bile duct-ligated livers do not promote hepatic fibrosis
Saito, J. M. (2003) · Hepatology Research · doi:10.1016/s1386-6346(02)00247-4 · Cited by 47 · see citing works
Altered Kupffer cell function in biliary obstruction
Minter, R. M., Fan, M., Sun, J., Niederbichler, A. D., Ipaktchi, K. R., Arbabi, S., Hemmila, M. R., Remick, D. G., Wang, S. C., & Su, G. L. (2005) · Surgery · doi:10.1016/j.surg.2005.04.001 · Cited by 41 · see citing works
Sakaida, I., Hironaka, K., Terai, S., & Okita, K. (2002) · Life Sciences · doi:10.1016/s0024-3205(02)02342-1 · Cited by 40 · see citing works
Giacometti, A., Cirioni, O., Ghiselli, R., Mocchegiani, F., D’Amato, G., Prete, M. S. D., Orlando, F., Kamysz, W., Lukasiak, J., Saba, V., et al. (2003) · Gut · doi:10.1136/gut.52.6.874 · Cited by 35 · see citing works
Maruiwa, M., Mizoguchi, A., Russell, G. J., Narula, N., Stronska, M., Mizoguchi, E., Rabb, H., Arnaout, M. A., & Bhan, A. K. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.9.4019 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
The gut-liver axis and the intersection with the microbiome
Tripathi, A., Debelius, J., Brenner, D. A., Karin, M., Loomba, R., Schnabl, B., & Knight, R. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0011-z · Cited by 1,480 · see citing works
Toll‐like receptors and adaptor molecules in liver disease: Update†
Seki, E., & Brenner, D. A. (2008) · Hepatology · doi:10.1002/hep.22306 · Cited by 722 · see citing works
The gut microbiome and liver cancer: mechanisms and clinical translation
Yu, L.-X., & Schwabe, R. F. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.72 · Cited by 634 · see citing works
Endogenous toll‐like receptor ligands and their biological significance
Yu, L., Wang, L., & Chen, S. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01127.x · Cited by 531 · see citing works
Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut
Seki, E., & Schnabl, B. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.219691 · Cited by 440 · see citing works
Gene Expression Profiles During Hepatic Stellate Cell Activation in Culture and In Vivo
Minicis, S. D., Seki, E., Uchinami, H., Kluwe, J., Zhang, Y., Brenner, D. A., & Schwabe, R. F. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.02.033 · Cited by 425 · see citing works
Redox mechanisms in hepatic chronic wound healing and fibrogenesis
Novo, E., & Parola, M. (2008) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-1-5 · Cited by 406 · see citing works
The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases
Soares, J., Pimentel‐Nunes, P., Roncon‐Albuquerque, R., & Leite-Moreira, A. F. (2010) · Hepatology International · doi:10.1007/s12072-010-9219-x · Cited by 369 · see citing works
The Yin and Yang of Toll-like receptors in cancer
Pradère, J., Dapito, D. H., & Schwabe, R. F. (2013) · Oncogene · doi:10.1038/onc.2013.302 · Cited by 332 · see citing works
Toll-like receptors as targets in chronic liver diseases
Mencin, A. M., Kluwe, J., & Schwabe, R. F. (2009) · Gut · doi:10.1136/gut.2008.156307 · Cited by 328 · see citing works
Microbiota-liver axis in hepatic disease
Chassaing, B., Etienne‐Mesmin, L., & Gewirtz, A. T. (2013) · Hepatology · doi:10.1002/hep.26494 · Cited by 329 · see citing works
Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease
Fouts, D. E., Torralba, M., Nelson, K. E., Brenner, D. A., & Schnabl, B. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.01.019 · Cited by 311 · see citing works
Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis
Guo, J., & Friedman, S. L. (2010) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-3-21 · Cited by 315 · see citing works
Characterization of time-related changes after experimental bile duct ligation
Georgiev, P., Jochum, W., Heinrich, S., Jang, J., Nocito, A., Dahm, F., & Clavien, P. (2008) · British journal of surgery · doi:10.1002/bjs.6050 · Cited by 249 · see citing works
Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis
Giannelli, V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i45.16795 · Cited by 237 · see citing works
Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice
Mazagova, M., Wang, L., Anfora, A. T., Wissmueller, M., Lesley, S. A., Miyamoto, Y., Eckmann, L., Dhungana, S., Pathmasiri, W., Sumner, S., et al. (2015) · The FASEB Journal · doi:10.1096/fj.14-259515 · Cited by 199 · see citing works
Contribution of Gut Bacteria to Liver Pathobiology
Son, G., Kremer, M., & Hines, I. N. (2010) · Gastroenterology Research and Practice · doi:10.1155/2010/453563 · Cited by 183 · see citing works
Self-citationToll-Like Receptors in Liver Fibrosis: Cellular Crosstalk and Mechanisms
Yang, L., & Seki, E. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00138 · Cited by 176 · see citing works
Toll-like receptors in pathophysiology of liver diseases
KIZILTAŞ, Ş. (2016) · World Journal of Hepatology · doi:10.4254/wjh.v8.i32.1354 · Cited by 176 · see citing works
Hrncir, T., Hrncirova, L., Kverka, M., Hromádka, R., Machova, V., Trckova, E., Kostovcikova, K., Králíčková, P., Krejsek, J., & Tlaskalová‐Hogenová, H. (2021) · Microorganisms · doi:10.3390/microorganisms9050957 · Cited by 179 · see citing works
Fei, N., Bruneau, A., Zhang, X., Wang, R., Wang, J., Rabot, S., Gérard, P., & Zhao, L. (2020) · mBio · doi:10.1128/mbio.03263-19 · Cited by 170 · see citing works
Anti-fibrogenic strategies and the regression of fibrosis
Kisseleva, T., & Brenner, D. A. (2011) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2011.02.011 · Cited by 169 · see citing works
Role of Toll-Like Receptors in Immune Activation and Tolerance in the Liver
Nakamoto, N., & Kanai∥, T. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00221 · Cited by 168 · see citing works
Periodontitis, chronic liver diseases, and the emerging oral‐gut‐liver axis
Albuquerque‐Souza, E., & Sahingur, S. E. (2022) · Periodontology 2000 · doi:10.1111/prd.12427 · Cited by 162 · see citing works
Toll-like Receptor 4 and Hepatic Fibrogenesis
Pradere, J.-P., Troeger, J., Dapito, D., Mencin, A., & Schwabe, R. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1255353 · Cited by 158 · see citing works
Son, G., Hines, I. N., Lindquist, J., Schrum, L. W., & Rippe, R. A. (2009) · Hepatology · doi:10.1002/hep.23186 · Cited by 152 · see citing works
Self-citationBMP-9 interferes with liver regeneration and promotes liver fibrosis
Breitkopf‐Heinlein, K., Meyer, C., König, C., Gaitantzi, H., Addante, A., Thomas, M., Wiercinska, E., Cai, C., Li, Q., Wan, F., et al. (2017) · Gut · doi:10.1136/gutjnl-2016-313314 · Cited by 150 · see citing works
Sheth, P., Santos, N. D., Seth, A., LaRusso, N. F., & Rao, R. K. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00582.2006 · Cited by 144 · see citing works
Role of TLR9 in hepatic stellate cells and experimental liver fibrosis
Gäbele, E., Mühlbauer, M., Dorn, C., Weiß, T. S., Froh, M., Schnabl, B., Wiest, R., Schölmerich, J., Obermeier, F., & Hellerbrand, C. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.08.096 · Cited by 141 · see citing works
The Nuclear Factor κB pathway: A link to the immune system in the radiation response
Hellweg, C. E. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.02.019 · Cited by 139 · see citing works
Regulation of wound healing and organ fibrosis by toll-like receptors
Huebener, P., & Schwabe, R. F. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.11.017 · Cited by 140 · see citing works
Toll-Like Receptor Signaling and Liver Fibrosis
Aoyama, T., Paik, Y., & Seki, E. (2010) · Gastroenterology Research and Practice · doi:10.1155/2010/192543 · Cited by 139 · see citing works
Toll‐like receptors and their role in gastrointestinal disease
Testro, A., & Visvanathan, K. (2009) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2009.05854.x · Cited by 134 · see citing works
Toll-like receptors, wound healing, and carcinogenesis
Kluwe, J., Mencin, A. M., & Schwabe, R. F. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0426-z · Cited by 133 · see citing works
Hartmann, P., Haimerl, M., Mazagova, M., Brenner, D. A., & Schnabl, B. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.07.099 · Cited by 118 · see citing works
Metagenomics of the Human Body
Nelson, K. E. (2010) · Springer eBooks · doi:10.1007/978-1-4419-7089-3 · Cited by 117 · see citing works
Yan, A. W. (2012) · World Journal of Hepatology · doi:10.4254/wjh.v4.i4.110 · Cited by 110 · see citing works
The intestinal microbiome and the leaky gut as therapeutic targets in alcoholic liver disease
Hartmann, P., Chen, W., & Schnabl, B. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00402 · Cited by 109 · see citing works
Liver Fibrosis Occurs Through Dysregulation of MyD88-Dependent Innate B-Cell Activity
Thapa, M., Chinnadurai, R., Velazquez, V. M., Tedesco, D., Elrod, E., Han, J., Sharma, P., Ibegbu, C., Gewirtz, A., Anania, F., et al. (2015) · Hepatology · doi:10.1002/hep.27761 · Cited by 101 · see citing works
The Gut-Liver Axis in Cholestatic Liver Diseases
Blesl, A., & Stadlbauer, V. (2021) · Nutrients · doi:10.3390/nu13031018 · Cited by 99 · see citing works
Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: An input for novel therapies
Frăsinariu, O. E., Ceccarelli, S., Alisi, A., Moraru, E., & Nobili, V. (2012) · Digestive and Liver Disease · doi:10.1016/j.dld.2012.11.010 · Cited by 97 · see citing works
Diet-induced gut dysbiosis and inflammation: Key drivers of obesity-driven NASH
Kang, G. G., Trevaskis, N. L., Murphy, A. J., & Febbraio, M. A. (2023) · iScience · doi:10.1016/j.isci.2022.105905 · Cited by 94 · see citing works
Roderburg, C., & Luedde, T. (2014) · Gut Microbes · doi:10.4161/gmic.29599 · Cited by 87 · see citing works
Zhang, X., Lau, H. C.-H., & Yu, J. Q. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2024.100018 · Cited by 94 · see citing works
Liao, R., Sun, T., Yi, Y., Wu, H., Li, Y., Wang, J., Zhou, J., Shi, Y., Cheng, Y., Qiu, S., et al. (2012) · Cancer Science · doi:10.1111/j.1349-7006.2012.02273.x · Cited by 83 · see citing works
Review article: the reversibility of cirrhosis
Sohrabpour, A. A., Mohamadnejad, M., & Malekzadeh, R. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12044 · Cited by 80 · see citing works
Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis
Maslennikov, R. V., Poluektova, E. A., Zolnikova, O. Y., Sedova, A., Курбатова, А. А., Shulpekova, Y. O., Dzhakhaya, N., Kardasheva, S. S., Nadinskaia, M. Y., Леонидовна, Б. Е., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216502 · Cited by 76 · 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
NAFLD and HBV interplay - related mechanisms underlying liver disease progression
Tourkochristou, E., Assimakopoulos, S. F., Thomopoulos, K., Marangos, M., & Triantos, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.965548 · Cited by 70 · see citing works
Cell Signals Influencing Hepatic Fibrosis
Cong, M., Iwaisako, K., Jiang, C., & Kisseleva, T. (2012) · International Journal of Hepatology · doi:10.1155/2012/158547 · Cited by 70 · see citing works
Toll-like receptor deficiency worsens inflammation and lymphedema after lymphatic injury
Zampell, J. C., Elhadad, S., Avraham, T., Weitman, E. S., Aschen, S. Z., Yan, A., & Mehrara, B. J. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00284.2011 · Cited by 68 · see citing works
Publisher Correction: The gut–liver axis and the intersection with the microbiome
Tripathi, A., Debelius, J., Brenner, D. A., Karin, M., Loomba, R., Schnabl, B., & Knight, R. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0031-8 · Cited by 68 · see citing works
Toll-like receptors as therapeutic targets in gastrointestinal diseases
Pimentel‐Nunes, P., Soares, J., Roncon‐Albuquerque, R., Dinis-Ribeiro, M. J., & Leite-Moreira, A. F. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728221003642027 · Cited by 66 · see citing works
Kanmani, P., & Kim, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01537 · Cited by 60 · see citing works
Mechanisms of Tissue Remodeling in Inflammatory Bowel Disease
Rieder, F., & Fiocchi, C. (2013) · Digestive Diseases · doi:10.1159/000353364 · Cited by 59 · see citing works
Starring role of toll-like receptor-4 activation in the gut-liver axis
Carotti, S. (2015) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v6.i4.99 · Cited by 57 · 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
Toll‐like receptor signaling in liver regeneration, fibrosis and carcinogenesis
Seki, E., Park, E., & Fujimoto, J. (2011) · Hepatology Research · doi:10.1111/j.1872-034x.2011.00822.x · Cited by 51 · see citing works
HIV and hepatitis C coinfection
Page, E. E., Nelson, M. R., & Kelleher, P. (2011) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e32834bbc71 · Cited by 51 · see citing works
Liu, Y., Li, ., Jin, Y., Zhao, L., Zhao, F., Feng, J., Li, A., & Wei, Y. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00963 · Cited by 50 · see citing works
Zhao, W., Wang, L., Yang, J.-L., Li, L., Xu, W., & Li, T. (2013) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2013.1613 · Cited by 41 · see citing works
Role of host genetics in fibrosis
Hold, G. L., Untiveros, P., Saunders, K. A., & El-Omar, E. M. (2009) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-2-6 · Cited by 40 · see citing works
A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells
Schnabl, B., Brandl, K., Fink, M., Groß, P., Taura, K., Gäbele, E., Hellerbrand, C., & Falk, W. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.07.150 · Cited by 37 · see citing works
Evans, T. I., Li, H., Schafer, J. L., Klatt, N. R., Hao, X., Traslavina, R. P., Estes, J. D., Brenchley, J. M., & Reeves, R. K. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv404 · Cited by 36 · see citing works
Small Bowel Transit and Altered Gut Microbiota in Patients With Liver Cirrhosis
Liu, Y., Jin, Y., Li, J., Zhao, L., Li, Z., Xu, J., Zhao, F., Feng, J., Chen, H., Fang, C., et al. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00470 · Cited by 35 · see citing works
Yao, H., & Li, J. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.219816 · Cited by 34 · see citing works
Pro- and Anti-fibrogenic Functions of Gram-Negative Bacterial Lipopolysaccharide in the Liver
Gandhi, C. R. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00130 · Cited by 34 · see citing works
Shi, W., Su, L., Li, Q., Sun, L., Lv, J., Li, J., & Cheng, B. (2014) · Tumor Biology · doi:10.1007/s13277-014-2268-3 · Cited by 34 · see citing works
Liu, J., Zhang, Z., Gao, J., Xie, J., Yang, L., & Hu, S. (2011) · Frontiers of Medicine · doi:10.1007/s11684-011-0111-4 · Cited by 30 · see citing works
Lin, H., Yang, Y., Tsai, T., Huang, C.-M., Huang, Y., Lee, F., Liu, T.-T., & Lee, S. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.09.026 · Cited by 29 · see citing works
Lin, Y.-C., Wang, F., Yang, Y., Chuang, Y.-T., & Huang, Y. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.01.132 · Cited by 28 · see citing works
Gut microbiome changes in Nonalcoholic fatty liver disease & alcoholic liver disease
Kwong, E. K., & Puri, P. (2020) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2020.02.18 · Cited by 28 · see citing works
Mohamadkhani, A. (2018) · Cancer Medicine · doi:10.1002/cam4.1550 · Cited by 26 · see citing works
Saito, S., Hata, K., Iwaisako, K., Yanagida, A., Takeiri, M., Tanaka, H., Kageyama, S., Hirao, H., Ikeda, K., Asagiri, M., et al. (2013) · Hepatology Research · doi:10.1111/hepr.12140 · Cited by 25 · see citing works
Cao, F., Zhang, Y., Li, W., Shimizu, K., Xie, H., & Zhang, C. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2017.12.023 · Cited by 25 · see citing works
Banerjee, A., & Farci, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168641 · Cited by 24 · see citing works
Ma, C.-Y., Chang, W.-E., Shi, G.-Y., Chang, B.-Y., Cheng, S.-E., Shih, Y.-T., & Wu, H. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1400923 · Cited by 24 · see citing works
Role of Endotoxemia in Causing Renal Dysfunction in Cirrhosis
Peng, J. L., Techasatian, W., Hato, T., & Liangpunsakul, S. (2019) · Journal of Investigative Medicine · doi:10.1136/jim-2019-001056 · Cited by 24 · see citing works
Pivotal role of Smad3 in a mouse model of T cell–mediated hepatitis
Kremer, M., Perry, A. W., Milton, R. J., Rippe, R. A., Wheeler, M. D., & Hines, I. N. (2007) · Hepatology · doi:10.1002/hep.21956 · Cited by 24 · see citing works
Self-citationNyström, J., Stenkvist, J., Häggblom, A., Weiland, O., & Nowak, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118643 · Cited by 23 · see citing works
Immunological Orchestration of Liver Fibrosis
Tanaka, H., Leung, P. S. C., Kenny, T. P., Gershwin, M. E., & Bowlus, C. L. (2012) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-012-8323-1 · Cited by 22 · see citing works
Endotoxin and CD14 in the progression of biliary atresia
Chou, M.-H., Chuang, J., Eng, H., Chen, C.-M., Wang, C.-H., Chen, C., & Lin, T. (2010) · Journal of Translational Medicine · doi:10.1186/1479-5876-8-138 · Cited by 22 · see citing works
Kanmani, P., Ansari, A., Villena, J., & Kim, H. (2019) · Journal of Immunology Research · doi:10.1155/2019/3876896 · Cited by 18 · see citing works
Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity
Chou, M.-H., Chuang, J., Eng, H., Tsai, P.-C., Hsieh, C., Liu, H.-C., Wang, C.-H., Lin, C.-Y., & Lin, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034903 · Cited by 17 · see citing works
Biliary fibrosis in microsurgical extrahepatic cholestasis in the rat
Sánchez‐Patán, F., Anchuelo, R., Corcuera, M. T., Casado, I., Gómez, F., Aller, M., Cruz, A., Alonso, M., & Árias, J. (2008) · Microsurgery · doi:10.1002/micr.20495 · Cited by 17 · see citing works
Vesković, M. N., Pejović, M., Šutulović, N., Hrnčić, D., Rašić-Marković, A., Stanojlović, O. P., & Mladenović, D. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137405 · Cited by 17 · see citing works
Thalidomide decreases intrahepatic resistance in cirrhotic rats
Yang, Y., Huang, Y., Lin, H., Lee, F., Lee, K., Chau, G., Loong, C., Lai, C., & Lee, S. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.160 · Cited by 16 · see citing works
What is the potential role of antifibrotic agents for the treatment of liver disease?
Schnabl, B., Scholten, D., & Brenner, D. A. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1200 · Cited by 15 · see citing works
Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment
Spanu, D., Pretta, A., Lai, E., Persano, M., Donisi, C., Mariani, S., Dubois, M., Migliari, M., Saba, G., Ziranu, P., et al. (2022) · World Journal of Hepatology · doi:10.4254/wjh.v14.i7.1319 · Cited by 14 · see citing works
Safari, F., Sharifi, M., Talebi, A., Mehranfard, N., & Ghasemi, M. (2023) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-023-02455-z · Cited by 12 · see citing works
Expression of Septin4 in Human Hepatic Stellate Cells LX-2 Stimulated by LPS
Sun, X., Yang, Y., Zhu, D., Qian, H., Duan, Y., He, X., Gu, X., Sun, W., & Zhu, Y. (2012) · Inflammation · doi:10.1007/s10753-012-9575-x · Cited by 12 · see citing works
Siddiqi, N. J., & Zargar, S. (2014) · Connective Tissue Research · doi:10.3109/03008207.2014.900551 · Cited by 11 · see citing works
Gastrointestinal Dysfunction in Chronic Liver Disease
Nguyen, D. H. N. Q. (2015) · Journal of Gastrointestinal & Digestive System · doi:10.4172/2161-069x.1000257 · Cited by 10 · see citing works
Smad3 signaling in the regenerating liver: implications for the regulation of IL-6 expression
Kremer, M., Son, G., Zhang, K., Moore, S. M., Norris, A., Manzini, G., Wheeler, M. D., & Hines, I. N. (2014) · Transplant International · doi:10.1111/tri.12322 · Cited by 9 · see citing works
Self-citationAnimal Models of Cutaneous and Hepatic Fibrosis
Smith, G. P. (2011) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-394596-9.00011-1 · Cited by 8 · see citing works
Overexpression of pim-3 and protective role in lipopolysaccharide-stimulated hepatic stellate cells
Liu, L. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i29.8858 · Cited by 8 · see citing works
Mendrick, D. L., & Daniels, K. K. (2007) · Biomarkers in Medicine · doi:10.2217/17520363.1.2.319 · Cited by 8 · see citing works
Regulation of hepatic Sirt1 expression and lipid metabolism through TNF receptor signaling
Hines, I. N., Stafford, S. B., Bradford, B. U., & Wheeler, M. D. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1627433 · Cited by 7 · see citing works
Self-citationHuang, C., Mei, S., Zhang, X., & Tian, X. (2023) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001883 · Cited by 8 · see citing works
- Authors
- Isayama, F., Hines, I. N., Kremer, M., Milton, R. J., Byrd, C. L., Perry, A. W., McKim, S. E., Parsons, C., Rippe, R. A., & Wheeler, M. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2006-06
- Volume
- 290
- Issue
- 6
- Pages
- G1318-G1328
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2020219616
- Cited by
- 123
- References
- 21
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 8 · 2017: 4 · 2016: 2 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 15
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- liver fibrosis, cholestatic liver disease, lipopolysaccharide signaling, CD14, endotoxemia, hepatic macrophages, bile duct ligation, LPS-binding protein, oxidative stress, 4-hydroxynonenal, alpha-smooth muscle actin, liver injury
- MeSH terms
- Animals, Cholestasis, Disease Models, Animal, Lipopolysaccharides, Liver, Liver Cirrhosis, Male, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Lipopolysaccharide Receptors, Mice
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
