The DOI matches its Crossref record; 40 of the 42 references it cites were found in a registry or an index.
Apoptotic Body Engulfment by a Human Stellate Cell Line Is Profibrogenic
Open accessAbstract
Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-beta (TGF-beta), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in alpha-smooth muscle actin (primary cells), TGF-beta1, and collagen alpha1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-beta1 and collagen alpha1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen alpha1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway.
Overview
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
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“Earlier in vitro studies reported that HSC line LX-1 is able to engulf apoptotic bodies of hepatocytes, which induced pro-fibrogenic activation in vitro via a nicotinamide adenine dinucleotide phosphate oxidase20 and phosphoinositide 3-kinase/p38 mitogen-activated protein kinase-dependent manner21.”
From Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis (2020) · cites this paper as [21]
In the citing paper
“Dying or damaged hepatocytes secrete damage-associated molecular patterns including high mobility group box 1 protein (HMGB1), osteopontin (SPP1), purinoceptor 14 (P2Y14) ligands, apoptotic bodies, microRNA (miRNA), and DNA that can be packaged into microvesicles and directly taken up by HSCs, leading to their activation into collagen-producing myofibroblasts (see “Cellular plasticity”, below) (23”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1112 · Cited by 3,166 · cited 3×
“Current concepts derived from developmental biology suggest that apoptosis and clearance of apoptotic bodies are evolutionary conserved processes to limit or even prevent inflammatory responses (Fadok et al, 1998; Savill, 2000).”
BackgroundMechanisms of phagocytosis in macrophages
Aderem, A., & Underhill, D. M. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.593 · Cited by 2,854
Role of Transforming Growth Factor β in Human Disease
Blobe, G. C., Schiemann, W. P., & Lodish, H. F. (2000) · New England Journal of Medicine · doi:10.1056/nejm200005043421807 · Cited by 2,453
Molecular Regulation of Hepatic Fibrosis, an Integrated Cellular Response to Tissue Injury
Friedman, S. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.4.2247 · Cited by 2,067
Self-citationProduct Differentiation by Analysis of DNA Melting Curves during the Polymerase Chain Reaction
Ririe, K. M., Rasmussen, R. P., & Wittwer, C. T. (1997) · Analytical Biochemistry · doi:10.1006/abio.1996.9916 · Cited by 1,663
Corpse clearance defines the meaning of cell death
Savill, J., & Fadok, V. A. (2000) · Nature · doi:10.1038/35037722 · Cited by 1,572
Hepatic lipocytes: the principal collagen-producing cells of normal rat liver.
Friedman, S. L., Roll, F. J., Boyles, J., & Bissell, D. M. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.24.8681 · Cited by 859
Self-citationHistory, Heterogeneity, Developmental Biology, and Functions of Quiescent Hepatic Stellate Cells
Geerts, A. (2001) · Seminars in Liver Disease · doi:10.1055/s-2001-17550 · Cited by 740
Fadok, V., de Cathelineau, A., Daleke, D. L., Henson, P., & Bratton, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m003649200 · Cited by 689
Transport and Storage of Vitamin A
Blomhoff, R., Green, M. H., Berg, T., & Norum, K. R. (1990) · Science · doi:10.1126/science.2218545 · Cited by 609
Cited by
Sorted by citations
Items 201–300 of 414
Marrocco, C., Rinalducci, S., Mohamadkhani, A., D’Amici, G. M., & Zolla, L. (2010) · PubMed Central · doi:10.2450/2010.017s · Cited by 31
Thiol redox systems and protein kinases in hepatic stellate cell regulatory processes
Brunati, A. M., Pagano, M. A., Bindoli, A., & Rigobello, M. P. (2010) · Free Radical Research · doi:10.3109/10715760903555836 · Cited by 31
“Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores [15]”
BackgroundBorensztajn, K., von der Thüsen, J. H., Peppelenbosch, M. P., & Spek, C. A. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00980.x · Cited by 31
“In addition, however, apoptotic hepatocytes are ingested by KCs leading to the release of TGF- and subsequent HSC activation [67, 68].”
BackgroundTargeting Hepatic Fibrosis in Autoimmune Hepatitis
Montaño‐Loza, A. J., Thandassery, R. B., & Czaja, A. J. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4254-7 · Cited by 30
“Quiescent hepatic stellate cells are activated by engulfing the apoptotic bodies of dying hepatocytes [65, 66], and they are transformed into myofibroblasts by TGF-b1, platelet-derived growth factor (PDGF), endothelial growth factor (EGF), and angiotensin II [37, 67–72] (Fig.”
BackgroundIsoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism
Biswas, A., Santra, S., Bishnu, D., Dhali, G. K., Chowdhury, A., & Santra, A. K. (2020) · International Journal of Hepatology · doi:10.1155/2020/6987295 · Cited by 30
Gieseler, R. K. H., Marquitan, G., Schlattjan, M., Sowa, J., Bechmann, L. P., Timm, J., Roggendorf, M., Gerken, G., Friedman, S. L., & Canbay, A. E. (2010) · Journal of Viral Hepatitis · doi:10.1111/j.1365-2893.2010.01362.x · Cited by 30
Self-citationLee, S. M. L., Schelcher, C., Laubender, R. P., Fröse, N., Thasler, R., Schiergens, T. S., Mansmann, U., & Thasler, W. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107567 · Cited by 30
Proteasome inhibition attenuates hepatic injury in the bile duct-ligated mouse
Anan, A., Baskin-Bey, E. S., Isomoto, H., Mott, J. L., Bronk, S. F., Albrecht, J. H., & Gores, G. J. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00126.2006 · Cited by 30
Self-citationSteatohepatitis and Apoptosis: Therapeutic Implications
Feldstein, A. E., & Gores, G. J. (2004) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2004.40573.x · Cited by 30
Self-citationEfferocytosis in liver disease
Shi, H., Moore, M. P., Wang, X., & Tabas, I. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2023.100960 · Cited by 30
Anatomy, pathophysiology and basic mechanisms of disease
Crawford, J. M., & Burt, A. D. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7020-3398-8.00001-5 · Cited by 32
Kumar, S., Rani, R., Karns, R. A., & Gandhi, C. R. (2018) · The FASEB Journal · doi:10.1096/fj.201802015r · Cited by 29
Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis
Hirsova, P., Böhm, F., Dohnalkova, E., Nožičková, B., Heikenwalder, M., Gores, G., & Weber, A. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2283-9 · Cited by 27
Self-citationMechanisms of liver fibrosis in metabolic syndrome
Mehal, W. (2023) · eGastroenterology · doi:10.1136/egastro-2023-100015 · Cited by 28
The multifaceted role of macrophages during acute liver injury
Hassan, G. S., Molina, M. F., & Shoukry, N. H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1237042 · Cited by 30
Disease-Specific Mechanisms of Fibrosis: Hepatitis C Virus and Nonalcoholic Steatohepatitis
van der Poorten, D., & George, J. (2008) · Clinics in Liver Disease · doi:10.1016/j.cld.2008.07.003 · Cited by 28
Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)
Subramanian, P., Hampe, J., Tacke, F., & Chavakis, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23136996 · Cited by 35
“Furthermore, uptake of apoptotic bodies deriving from hepatocyte death also causes human HSC activation [70,78].”
BackgroundStructure, Function, and Responses to Injury
Crawford, J. M., Bioulac‐Sage, P., & Hytiroglou, P. (2017) · Elsevier eBooks · doi:10.1016/b978-0-7020-6697-9.00001-7 · Cited by 28
Liebig, S., Stöckmann, N., Geier, A., Rau, M., Schattenberg, J. M., Bahr, M. J., Manns, M. P., Jaeckel, E., Schulze‐Osthoff, K., & Bantel, H. (2019) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000066 · Cited by 27
The plasticity of p19ARF null hepatic stellate cells and the dynamics of activation
Proell, V., Mikula, M., Fuchs, E., & Mikulits, W. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.12.009 · Cited by 27
Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression
Amengual, J., Alay, A., Vaquero, J., Gonzalez‐Sanchez, E., Bertrán, E., Sánchez, A., Herrera, B. M., Meyer, K. R., Maus, M., Serrano, M., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07063-0 · Cited by 27
“The process occurs through a combination of different events: hepatocyte damage [2], in fl ammation [3], and activation of the hepatic stellate cells (HSC) into myo fi broblasts, the main producers of extracellular matrix (ECM) proteins [4, 5].”
IRS2 and PTP1B: Two opposite modulators of hepatic insulin signalling
Valverde, Á. M., & González‐Rodríguez, Á. (2011) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2011.557386 · Cited by 25
“The enhanced apoptosis associated with hepatic insulin resistance may lead to activation of hepatic stellate cells (HSC) either by the engulfment of apoptotic cells (Canbay et al., 2003b) or by a direct effect of Kupffer cells following”
BackgroundInfluentialBioconjugation of Oligonucleotides for Treating Liver Fibrosis
Ye, Z., Houssein, H. S. H., & Mahato, R. I. (2007) · Oligonucleotides · doi:10.1089/oli.2007.0097 · Cited by 26
Caspase Inhibitors for the Treatment of Hepatitis C
Masuoka, H. C., Guicciardi, M. E., & Gores, G. J. (2009) · Clinics in Liver Disease · doi:10.1016/j.cld.2009.05.010 · Cited by 26
Self-citationWu, R., Nakatsu, G., Zhang, X., & Yu, J. Q. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1125883 · Cited by 26
“[77] Likewise, hepatic stellate cells engulf hepatocyte apoptotic bodies to promote liver fibrosis.[78] Collectively, these studies indicate that both Kupffer”
BackgroundEffect of Alcohol on Viral Hepatitis and Other Forms of Liver Dysfunction
Balasubramanian, S., & Kowdley, K. V. (2005) · Clinics in Liver Disease · doi:10.1016/j.cld.2004.10.004 · Cited by 26
Lee, K.-C., Chan, C., Yang, Y.-Y., Hsieh, Y., Huang, Y.-H., & Lin, H.-C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077817 · Cited by 25
“The apoptotic bodies from hepatocytes engulfed by HSCs or KCs activate HSCs [40] and KCs [41], respectively.”
BackgroundInfluentialMoriya, T., Naito, H., Ito, Y., & Nakajima, T. (2009) · Journal of Occupational Health · doi:10.1539/joh.k9001 · Cited by 25
The pathogenesis of liver disease in the setting of HIV–hepatitis B virus coinfection
Iser, D. M., & Lewin, S. R. (2009) · Antiviral Therapy · doi:10.1177/135965350901400207 · Cited by 25
“Once activated, HSCs are important in the formation of the extracellular matrix and collagen, as well as producing proinflammatory cytokines and phagocytosing apoptotic bodies, which are themselves fibrogenic [86].”
BackgroundMetabolic injury of hepatocytes promotes progression of NAFLD and AALD
Carvalho-Gontijo, R., Han, C., Zhang, L., Zhang, V., Hosseini, M., Mekeel, K., Schnabl, B., Loomba, R., Karin, M., Brenner, D. A., et al. (2022) · Seminars in Liver Disease · doi:10.1055/s-0042-1755316 · Cited by 23
Carbon Tetrachloride-Induced Hepatotoxicity*
Fujimoto, J., & Iimuro, Y. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-046884-6.01018-6 · Cited by 24
Akyıldız, M., Günşar, F., Nart, D., Sahin, O., Yılmaz, F., Akay, S., Ersöz, G., Karasu, Z. A., İlter, T., Batur, Y., et al. (2010) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e328331a596 · Cited by 24
Sepúlveda‐Crespo, D., Resino, S., & Martínez, I. (2021) · Drugs · doi:10.1007/s40265-020-01458-x · Cited by 23
Hepatocyte-specific Prominin-1 protects against liver injury-induced fibrosis by stabilizing SMAD7
Lee, H., Yu, D., Bahn, M., Kwon, Y.-J., Um, M. J., Yoon, S. Y., Kim, K., Lee, M., Jo, S.-J., Lee, S., et al. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00831-y · Cited by 25
Ganesan, M., Poluektova, L. Y., Enweluzo, C., Kharbanda, K. K., & Osna, N. A. (2018) · Biomolecules · doi:10.3390/biom8040113 · Cited by 23
“Our data are in line with already published pro-fibrotic effects of AB engulfment by HSC [38] and pro-fibrotic activation of HSC with AB from Con1-bearing (HCV genotype 1) Huh cells that express only non-structural HCV proteins [7].”
ResultCanbakan, B., Şentürk, H., Canbakan, M., Toptaş, T., Tabak, Ö., Balcı, H., Olgaç, V., & Özbay, G. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.09.88 · Cited by 22
Effect of Immunosuppressive Agents on Hepatocyte Apoptosis Post-Liver Transplantation
Lim, E. J., Chin, R. A. D., Nachbur, U., Silke, J., Jia, Z., Angus, P., & Torresi, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138522 · Cited by 23
“Cyclosporine has been found to cause apoptosis of renal vascular endothelial cells[7], and fibrosis of the renal tubulointerstitium by upregulating TGF-β expression[18], raising concerns that similar effects may occur in the liver.”
BackgroundKovalic, A. J., Satapathy, S. K., & Chalasani, N. (2018) · Hepatology International · doi:10.1007/s12072-018-9854-1 · Cited by 25
Yanguas, S. C., da Silva, T. C., Pereira, I. V. A., Maes, M., Willebrords, J., Shestopalov, V. I., Goes, B., Nogueira, M. S., de Castro, I. A., Romualdo, G. R., et al. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2255-3 · Cited by 22
Antifibrogenic Effect of IFN- α 2b on Hepatic Stellate Cell Activation by Human Hepatocytes
Giannelli, G., Bergamini, C., Marinosci, F., Fransvea, E., Napoli, N., Maurel, P., Dentico, P., & Antonaci, S. (2006) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2006.26.301 · Cited by 23
Alcohol and HIV-Derived Hepatocyte Apoptotic Bodies Induce Hepatic Stellate Cell Activation
New‐Aaron, M., Dagur, R. S., Koganti, S. S., Ganesan, M., Wang, W., Makarov, E., Ogunnaike, M., Kharbanda, K. K., Poluektova, L. Y., & Osna, N. A. (2022) · Biology · doi:10.3390/biology11071059 · Cited by 21
“Previous studies identified the involvement of p38 MAPK in the activation of HSC [71].”
BackgroundYang, H., Guo, F.-Y., Lin, Y.-C., Wu, Y., Nan, J., Jin, C. H., & Lian, L. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106723 · Cited by 21
Al-Jammas, S., & Al–Saraj, A. (2020) · Al-mağallaẗ al-ʻirāqiyyaẗ li-l-ʻulūm al-bayṭariyyaẗ/Iraqi journal of veterinary sciences · doi:10.33899/ijvs.2020.163564 · Cited by 21
Cross-talk between hepatic stellate cells and T lymphocytes in liver fibrosis
Li, H., Ding, P., Peng, B., & Ming, Y. (2021) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2021.04.007 · Cited by 21
Pathil, A., Mueller, J., Ludwig, J. M., Wang, J., Warth, A., Chamulitrat, W., & Stremmel, W. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12837 · Cited by 20
“In addition to chronic inflammation, phagocytosis of hepatocellular apoptotic bodies by hepatic stellate cells was described to be another important stimulus for fibrogenic activation with subsequent matrix production (Canbay et al., 2003; Malhi and Gores, 2008).”
BackgroundShigekawa, M., Takehara, T., Kodama, T., Hikita, H., Shimizu, S., Li, W., Miyagi, T., Hosui, A., Tatsumi, T., Ishida, H., et al. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.02.105 · Cited by 21
Engulfment of Necrotic Acinar Cells by Pancreatic Stellate Cells Inhibits Pancreatic Fibrogenesis
Tahara, J., Shimizu, K., & Shiratori, K. (2008) · Pancreas · doi:10.1097/mpa.0b013e318160a5cb · Cited by 20
“9,22,25Y28 The characteristic feature of PSCs is quite similar to that of HSCs, and recent studies have demonstrated that HSCs have a phagocytic activity.(8,29) It has been reported that engulfment of apoptotic HepG2 cells, a well-differentiated human hepatoma cell line, by primary or immortalized HSCs is indicated by…”
BackgroundSmid, V. (2020) · Vnitřní lékařství · doi:10.36290/vnl.2020.078 · Cited by 19
Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes
Lee, T., Lin, Y., & Huang, Y. (2011) · Liver International · doi:10.1111/j.1478-3231.2011.02485.x · Cited by 19
“Although classic concepts suggest that apoptosis is non-inflammatory, emerging data have shown that hepatocyte apoptosis may contribute to liver inflammation and fibrosis (6, 7).”
BackgroundMethodHepatic Fibrosis and Cirrhosis
Rockey, D. C., & Friedman, S. L. (2006) · Elsevier eBooks · doi:10.1016/b978-1-4160-3258-8.50011-5 · Cited by 19
Self-citationCell death mechanisms in human chronic liver diseases: a far cry from clinical applicability
Mazzolini, G. D., Sowa, J., & Canbay, A. E. (2016) · Clinical Science · doi:10.1042/cs20160035 · Cited by 18
Self-citationPET/SPECT Molecular Probes for the Diagnosis and Staging of Nonalcoholic Fatty Liver Disease
Shao, T., Josephson, L., & Liang, S. H. (2019) · Molecular Imaging · doi:10.1177/1536012119871455 · Cited by 18
“The TGF-b is also a robust fibrogenic signal marker in the liver.(10)”
BackgroundOverexpression of Mcl-1 Attenuates Liver Injury and Fibrosis in the Bile Duct–Ligated Mouse
Kahraman, A., Mott, J. L., Bronk, S. F., Werneburg, N. W., Barreyro, F. J., Guicciardi, M. E., Akazawa, Y., Braley, K. E., Craig, R. W., & Gores, G. J. (2008) · Digestive Diseases and Sciences · doi:10.1007/s10620-008-0583-5 · Cited by 18
“The cellular remnants of apoptotic hepatocytes can be phagocytosed by either Kupffer and/or stellate cells [43, 44].”
Self-citationWound healing and local neuroendocrine regulation in the injured liver
Ebrahimkhani, M. R., Elsharkawy, A. M., & Mann, D. A. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s146239940800063x · Cited by 18
Communication initiated by hepatocytes: The driver of HSC activation and liver fibrosis
Lan, R., Lin, J., Chen, S., Lü, Z., Gong, Y., Tan, S., Liu, X., & He, W. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000753 · Cited by 18
“[118] Based on this study, Zhan and colleagues reported increased production of superoxide in HSCs after phagocytosis of HC-derived apoptotic bodies.”
Zhao, H., Zhang, X., Lu, X.-Y., Yu, S.-R., Wang, X., Zou, Y., Zuo, Z.-Y., Liu, D., & Zhou, B.-G. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00283 · Cited by 17
“It is known Frontiers in Pharmacology | www.frontiersin.org 6 March 2018 | Volume 9 | Article 283 that these changes are closely related to progression of liver disease (Canbay et al., 2003; Feldstein et al., 2003; Grivennikov et al., 2010).”
BackgroundGhost messages: cell death signals spread
Zhang, M., Lin, Y., Chen, R., Yu, H., Li, Y., Chen, M., Dou, C., Yin, P., Zhang, L., & Tang, P. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-022-01004-0 · Cited by 18
“The engulfment of ApoBDs by HSCs is profibrogenic, as evidenced by upregulated profibrotic genes, such as COL1A1, TGF-β1, TIMP1, TIMP2 and α-SMA, and a myofibroblast morphology with collagen producing [178].”
BackgroundStellate Cells and Hepatic Fibrosis
Hasegawa, D., Wallace, M. C., & Friedman, S. L. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800134-9.00004-x · Cited by 17
Self-citationPathogenesis of Nonalcoholic Fatty Liver Disease
Machado, M. V., & Diehl, A. M. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-37591-7.00025-2 · Cited by 17
Byakangelicin protects against carbon tetrachloride–induced liver injury and fibrosis in mice
Li, X., Shao, S., Li, H., Bi, Z., Zhang, S., Wei, Y., Bai, J., Zhang, R., Ma, X., Ma, B., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15493 · Cited by 17
Biomimetic nanoparticles for targeted therapy of liver disease
Vijayan, V., Unagolla, J. M., Panchal, D., Okoh, J. E., Menon, S. S., & Menon, J. U. (2025) · RSC Pharmaceutics · doi:10.1039/d5pm00044k · Cited by 20
Tu, Y., Chen, D., Pan, T., Chen, Z., Xu, J., Jin, L., Sheng, L., Jin, X., Wang, X., Lan, X., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119698 · Cited by 16
van Son, K. C., Verschuren, L., Hanemaaijer, R., Reeves, H. L., Takkenberg, R. B., Drenth, J. P. H., Tushuizen, M. E., & Holleboom, A. G. (2023) · Cancers · doi:10.3390/cancers15041308 · Cited by 17
“Additionally, hepatocyte apoptosis adds to the pro-inflammatory environment and the recruitment of monocytes into the liver [58–60] and the release of hepatocyte apoptotic bodies can induce the activation of macrophages and HSCs [48,61].”
BackgroundThe impact of emricasan on chronic liver diseases: current data
Lekakis, V., & Cholongitas, Ε. (2022) · Clinical Journal of Gastroenterology · doi:10.1007/s12328-021-01585-2 · Cited by 16
“Notably, this procedure is associated with the transformation of the HSCs to an active phenotype which is typically positive for alpha smooth muscle actin (a-SMA) and are characterized by increased fibrogenic activity via the production of collagen Ia and transforming growth factor beta 1 (TGF-β1) [16].”
BackgroundApoptosis markers in liver biopsy of nonalcoholic steatohepatitis in pediatric patients
Valva, P., Matteo, E. D., Galoppo, M., Pedreira, A., Giacove, G., Lezama, C., Marco, I., Galoppo, M. C., & Preciado, M. V. (2008) · Human Pathology · doi:10.1016/j.humpath.2008.04.022 · Cited by 16
Siddiqui, H., Deo, N., Rutledge, M. T., Williams, M. J. A., Redpath, G., & McCormick, S. P. A. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.319344 · Cited by 17
“71 Indeed, HepG2 cells seem not capable of efferocytosis, 72 ruling out this process as an Lp(a)/apo(a) uptake route.”
BackgroundCrosstalk in extrahepatic and hepatic system in NAFLD / NASH
Duan, Y., Yang, Y. Z., Zhao, S., Bai, Y., Yao, W., Gao, X., & Yin, J. (2024) · Liver International · doi:10.1111/liv.15967 · Cited by 16
Aliskiren attenuates chronic carbon tetrachloride–induced liver injury in mice
Lee, K., Chan, C., Yang, Y., Hsieh, Y., Huang, Y., & Lin, H. (2012) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2012.02725.x · Cited by 15
Stellate Cells in the Tumor Microenvironment
Roife, D., Sarcar, B., & Fleming, J. B. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-44518-8_6 · Cited by 15
Differential effect of interleukin-10 on hepatocyte apoptosis
Santiago-Lomeli, M., Gómez-Quiroz, L. E., Ortíz-Ortega, V. M., Kershenobich, D., & Gutiérrez‐Ruíz, M. C. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.10.048 · Cited by 15
Bianca, C., Sidhartha, E., Tiribelli, C., El-Khobar, K. E., & Sukowati, C. H. C. (2022) · World Journal of Hepatology · doi:10.4254/wjh.v14.i5.866 · Cited by 15
TLRs in Hepatic Cellular Crosstalk
Bigorgne, A., & Crispe, I. N. (2010) · Gastroenterology Research and Practice · doi:10.1155/2010/618260 · Cited by 14
“As a sensor for cell injury, HSCs phagocytose apoptotic hepatocyte bodies with subsequent regulation of TGF-β and collagen-α1 mRNA [25].”
Macrophages and scavenger receptors in obesity‐associated non‐alcoholic liver fatty disease (NAFLD)
Petersen, S. K., Bilkei‐Gorzo, O., Govaere, O., & Härtlová, A. (2020) · Scandinavian Journal of Immunology · doi:10.1111/sji.12971 · Cited by 14
Activin A in Nonalcoholic Fatty Liver Disease
Yndestad, A., Haukeland, J. W., Dahl, T. B., Halvorsen, B. L., & Aukrust, P. (2011) · Vitamins and hormones · doi:10.1016/b978-0-12-385961-7.00015-9 · Cited by 14
“Furthermore, apoptotic hepatocytes may be ingested by Kupffer cells and HSC which subsequently release fibrogenic cytokines such as TGF-b (Canbay et al., 2003; Fadok et al., 1998).”
BackgroundHepatic Myofibroblasts: A Heterogeneous and Redox-Modulated Cell Population in Liver Fibrogenesis
Bocca, C., Protopapa, F., Foglia, B., Maggiora, M., Cannito, S., Parola, M., & Novo, E. (2022) · Antioxidants · doi:10.3390/antiox11071278 · Cited by 14
Isayama, F., Moore, S. M., Hines, I. N., & Wheeler, M. D. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.02.006 · Cited by 13
“gld mice given chronic ethanol, yet fibrosis is blunted in Fas mutant (lpr) mice after bile duct ligation.(30) Although our data affirm a significant relation between Fas-mediated apoptosis and liver fibrogenesis, these data highlight the important mechanistic differences in the pathogenesis between the various rodent…”
BackgroundInflammatory and Non-Inflammatory Mechanisms Controlling Cirrhosis Development
Sánchez, P. S., Rigual, M. D. M., & Djouder, N. (2021) · Cancers · doi:10.3390/cancers13205045 · Cited by 13
“Moreover, fibroblastic cells reportedly detect the apoptotic bodies released by dead hepatocytes, triggering the upregulation of TGF-β1 and the secretion of collagen type I [90,91].”
BackgroundYamashita, M., Honda, A., Shimoyama, S., Umemura, M., Ohta, K., Chida, T., Noritake, H., Kurono, N., Ichimura‐Shimizu, M., Tsuneyama, K., et al. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2023.103027 · Cited by 13
Wang, Y., Shi, C., Guo, J., Zhang, Y., & Gong, Z. (2023) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2023.00132 · Cited by 13
Inflammation and Hepatic Fibrosis, Then Hepatocellular Carcinoma
Kwon, O. S., Choi, S. H., & Kim, J. H. (2015) · Korean Journal of Gastroenterology · doi:10.4166/kjg.2015.66.6.320 · Cited by 13
Rasineni, K., Lee, S. M. L., McVicker, B. L., Osna, N. A., Casey, C. A., & Kharbanda, K. K. (2020) · Biology · doi:10.3390/biology10010019 · Cited by 13
“Most important is its role in the phagocytosis of apoptotic bodies [21,22], which by precluding their uptake by the nonparenchymal cells, prevents activation of Kupffer/hepatic stellate cells and liver damage progression [54,55].”
BackgroundDay, C. (2006) · Medicine · doi:10.1053/j.mpmed.2006.10.003 · Cited by 13
Bujak, M., Ratkaj, I., Markova-Car, E., Jurišić, D., Horvatić, A., Vučinić, S., Lerga, J., Lončar, M. B., Pavelić, K., & Pavelić, S. K. (2015) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2015.00068 · Cited by 12
“Moreover, during wound healing, phagocyte apoptotic cells and activate TGF-β1, a central mediator of fibrosis (Canbay et al., 2003).”
BackgroundEvolving paradigm of treatment for autoimmune hepatitis
Czaja, A. J. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1319764 · Cited by 12
“Angiotensin II is produced by HSCs, and it enhances the activity of NOXs, promotes the generation of ROS, and increases the expression of collagen-producing genes.”
BackgroundInfluentialInflammation During Virus Infection: Swings and Roundabouts
Bhattacharyya, S. (2020) · Springer eBooks · doi:10.1007/978-981-15-1045-8_3 · Cited by 13
Tang, Y., Ma, N., Luo, H., Chen, S., & Yu, F. (2020) · The Journal of Biochemistry · doi:10.1093/jb/mvaa013 · Cited by 12
Tang, W.-C., Chang, Y.-W., Che, M., Wang, M., Lai, K., Fueger, P. T., Huang, W., Lin, S., & Lai, K. K. Y. (2021) · Current Molecular Pharmacology · doi:10.2174/1874467214666210412144416 · Cited by 11
Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
John, K., Franck, M., Aoua, S. A., Rau, M., Huber, Y., Schattenberg, J. M., Geier, A., Bahr, M. J., Wedemeyer, H. H., Schulze‐Osthoff, K., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11154394 · Cited by 11
“Inflammation triggers monocyte recruitment and hepatocellular apoptosis which results in stellate cell activation and fibrogenesis [37,38].”
BackgroundKharbanda, K. K., Chokshi, S., Tikhanovich, I., Weinman, S. A., New‐Aaron, M., Ganesan, M., & Osna, N. A. (2023) · Biology · doi:10.3390/biology12020255 · Cited by 11
“HSC activation after ABs engulfment has previously been observed [127].”
BackgroundNew‐Aaron, M., Koganti, S. S., Ganesan, M., Kanika, S., Kumar, V. S., Wang, W., Makarov, E., Kharbanda, K. K., Poluektova, L. Y., & Osna, N. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065346 · Cited by 11
“Unlike other studies, which utilized the UV method to generate hepatocyte ABs [15,16], in the current study, we generated ABs from acetaldehyde and HIV-treated hepatocyte-like cells (RLW cells) [11].”
MethodValva, P., Rios, D. A., Casciato, P. C., Gadano, A. C., Galdame, O., Müllen, E., Bertot, G. M., Matteo, E. D., & Preciado, M. V. (2018) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000001079 · Cited by 11
Han, J. H., Kim, O., Lee, S. C., Kim, K., Park, J. H., Lee, J. I., Lee, K. H., Hong, H., Seo, H., Choi, H. J., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246302 · Cited by 11
“Several studies have validated that a pro-fibrogenic response occurs when the HSCs engulf the apoptotic bodies that are ejected from the hepatocytes [43,44].”
BackgroundM1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice
Rachakonda, V. P., Jadeja, R. N., Urrunaga, N. H., Shah, N., Ahmad, D., Cheng, K., Twaddell, W. S., Raufman, J., & Khurana, S. (2015) · Scientific Reports · doi:10.1038/srep14110 · Cited by 11
Malhi, H., & Gores, G. J. (2011) · Wiley eBooks · doi:10.1002/9781119950509.ch8 · Cited by 11
Self-citationInterleukin-1 family cytokines in liver cell death: a new therapeutic target for liver diseases
Udomsinprasert, W. (2023) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2023.2285763 · Cited by 10
“Besides this, the development of hepatic fibrosis has been linked to persistent liver cell death [4, 5].”
BackgroundMa, Z.-J., Qiu, Y., Yu, Z.-W., Song, T., Hu, Y., Peng, A., & Qi, R. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.12.016 · Cited by 10
Wei, X., Wei, H., Lin, W., Hu, Z., & Zhang, J. (2017) · Medicine · doi:10.1097/md.0000000000006807 · Cited by 10
Fahmy, H., & Mohammed, F. (2020) · Human & Experimental Toxicology · doi:10.1177/0960327120946470 · Cited by 10
“Canbay et al.42 clarified that the engulfment of apoptotic hepatocytes by HSC lines induced their activation with subsequent profibrogenic response and also the occurrence of oxidative stress in the hepatic tissue, and activated HSCs and the Kupffer cells.43,44 The spectral region 1800–1500 cm 1 corresponds primarily…”
BackgroundSaponara, I., Caruso, E. A., Cofano, M., Nunzio, V. D., Pinto, G., Centonze, M., & Notarnicola, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020512 · Cited by 9
Apoptotic cell death takes its toll
Torok, N. J. (2007) · Hepatology · doi:10.1002/hep.21968 · Cited by 9
Self-citation
Metadata
- Authors
- Canbay, A., Taimr, P., Torok, N., Higuchi, H., Friedman, S., & Gores, G. J.
- Affiliations
- Mayo Clinic (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Gores, Gregory J
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 83
- Issue
- 5
- Pages
- 655-663
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W2089907961
- Cited by
- 417
- References
- 42
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 13 · 2023: 23 · 2022: 15 · 2021: 19 · 2020: 29 · 2019: 10 · 2018: 20 · 2017: 31 · 2016: 13 · 2015: 11 · 2014: 33 · 2013: 13 · 2012: 18
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- US-UK Fulbright Commission
- Deutscher Akademischer Austauschdienst
- National Institutes of Health (DK 41876, DK56621)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK37430, DK 56621, DK-41876)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- hepatic stellate cells, hepatocyte apoptosis, liver fibrosis, TGF-β1, stellate cell activation, PI3K signaling, p38 MAPK signaling, chronic liver disease
- MeSH terms
- Cell Line, Humans, Liver Cirrhosis, Microtubules, RNA, Messenger, Nocodazole, Transforming Growth Factor beta, Apoptosis, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinases, Hepatocytes, Collagen Type I, p38 Mitogen-Activated Protein Kinases, Transforming Growth Factor beta1
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
