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Volumn 3, Issue 4, 2015, Pages 291-305

TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis: Updated

Author keywords

Hepatic stellate cells; Liver fibrosis; Myofibroblasts; TGF

Indexed keywords


EID: 84976506290     PISSN: None     EISSN: 2167485X     Source Type: Journal    
DOI: 10.1007/s40139-015-0089-8     Document Type: Review
Times cited : (32)

References (128)
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    • This paper convincingly shows participation of hepatocyte TGF-β signaling in the generation of a NASH phenotype in mice fed a high fat diet
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    • This paper shows that TAK1 is a critical TGF-β signaling regulator in hepatocytes that reduces pro-apoptotic activity by activating cell survival pathways. Its abrogation leads to massive TGF-β mediated hepatocyte death, proliferative activity and inflammation mediated HCC development
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    • −/− mice with lentiviral-GFP under the control of a hepatocyte-specific promoter. With that approach, the authors show that apoptosis and phagocytosis of hepatocytes directly induce HSC activation and initiation of fibrosis, and that NOX2, the phagocytic NADPH oxidase, plays a key role in this process
    • −/− mice with lentiviral-GFP under the control of a hepatocyte-specific promoter. With that approach, the authors show that apoptosis and phagocytosis of hepatocytes directly induce HSC activation and initiation of fibrosis, and that NOX2, the phagocytic NADPH oxidase, plays a key role in this process
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    • The study shows that hepatocytes under stress send out signals termed Damage-associated molecular patterns to initiate cellular reactions in injured liver tissue; in this case HMGB1, which amplifies neutrophil-mediated injury via its receptor RAGE
    • • Huebener P, Pradere J, Hernandez C, et al. (2015) The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis. 125:539–550. doi:10.1172/JCI76887.DAMP. The study shows that hepatocytes under stress send out signals termed Damage-associated molecular patterns to initiate cellular reactions in injured liver tissue; in this case HMGB1, which amplifies neutrophil-mediated injury via its receptor RAGE
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    • Signals from dying hepatocytes trigger growth of liver progenitors
    • The study similarly shows that dying hepatocytes overexpress Hh ligands, which provide a survival signal for progenitor cells and myofibroblasts thus triggering wound healing/fibrogenesis
    • • Jung Y, Witek RP, Syn W-K, et al. (2010) Signals from dying hepatocytes trigger growth of liver progenitors. Gut 59:655–665. doi:10.1136/gut.2009.204354. The study similarly shows that dying hepatocytes overexpress Hh ligands, which provide a survival signal for progenitor cells and myofibroblasts thus triggering wound healing/fibrogenesis
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    • Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice
    • An interesting study using lineage tracing to confirm that there is no change of the morphology and no expression of EMT markers in hepatocytes of CCl4-treated mice challenging the concept that hepatocytes can undergo EMT
    • •• Taura K, Miura K, Iwaisako K, et al. (2010) Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice. Hepatology 51:1027–1036. doi:10.1002/hep.23368. An interesting study using lineage tracing to confirm that there is no change of the morphology and no expression of EMT markers in hepatocytes of CCl4-treated mice challenging the concept that hepatocytes can undergo EMT
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    • Inhibitory effect of bone morphogenetic protein-7 on hepatic fibrosis in rats
    • The study shows the ability of BMP-7 to attenuate liver fibrosis via inhibition of TGF-β1 signaling
    • • Wang S-L, Yang C, Qi X-L, et al. (2013) Inhibitory effect of bone morphogenetic protein-7 on hepatic fibrosis in rats. Int J Clin Exp Pathol 6:897–903. The study shows the ability of BMP-7 to attenuate liver fibrosis via inhibition of TGF-β1 signaling
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    • • Kim S, Lim JH, Woo CH (2013) ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation. Am J Pathol 183:1758–1768. doi:10.1016/j.ajpath.2013.08.014. Interestingly, this study shows that ERK5 inhibition can antagonize TGF-β-mediated fibrogenic signaling through Smad3 acetylation instead through Smad3 phosphorylation
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    • A good study that expand our information about the specific roles that Smad2 and Smad3 play in organ fibrosis and confirm the results of Zhang et al (2014) in the liver
    • • Duan W-J, Yu X, Huang X-R, et al. (2014) Opposing roles for Smad2 and Smad3 in peritoneal fibrosis in vivo and in vitro. Am J Pathol 184:2275–2284. doi:10.1016/j.ajpath.2014.04.014 A good study that expand our information about the specific roles that Smad2 and Smad3 play in organ fibrosis and confirm the results of Zhang et al (2014) in the liver
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    • Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs
    • An elegant study that used Cre/Loxp technique to specifically target αv integrin in different organs. The results show that αv integrin depletion is effective in protecting the mice against CCl4-induced liver fibrosis and attentuated also renal and pulmonary fibrosis, highlighting αv integrin as general therapeutic target in variant fibrotic diseases
    • •• Henderson NC, Arnold TD, Katamura Y, et al. (2013) Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med 19:1617–24. doi:10.1038/nm.3282. An elegant study that used Cre/Loxp technique to specifically target αv integrin in different organs. The results show that αv integrin depletion is effective in protecting the mice against CCl4-induced liver fibrosis and attentuated also renal and pulmonary fibrosis, highlighting αv integrin as general therapeutic target in variant fibrotic diseases
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* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.