Epithelial-mesenchymal transition in liver fibrosis (Review)
- Authors:
- Ya‑Lei Zhao
- Rong‑Tao Zhu
- Yu‑Ling Sun
-
Affiliations: Department of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary and Pancreatic Diseases, School of Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China - Published online on: January 25, 2016 https://doi.org/10.3892/br.2016.578
- Pages: 269-274
This article is mentioned in:
Abstract
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|
Bi WR, Jin CX, Xu GT and Yang CQ: Effect of alendronate sodium on the expression of mesenchymal-epithelial transition markers in mice with liver fibrosis. Exp Ther Med. 5:247–252. 2013.PubMed/NCBI | |
|
Deng YH, Pu CL, Li YC, Zhu J, Xiang C, Zhang MM and Guo CB: Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia. Dig Dis Sci. 56:731–740. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Yoshida K and Matsuzaki K: Differential regulation of TGF-β/Smad signaling in hepatic stellate cells between acute and chronic liver injuries. Front Physiol. 3:532012. View Article : Google Scholar : PubMed/NCBI | |
|
Moreno-Alvarez P, Sosa-Garrocho M, Briones-Orta MA, González-Espinosa C, Medina-Tamayo J, Molina-Jijón E, Pedraza-Chaverri J and Macías-Silva M: Angiotensin II increases mRNA levels of all TGF-beta isoforms in quiescent and activated rat hepatic stellate cells. Cell Biol Int. 34:969–978. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Lee YS and Jeong WI: Retinoic acids and hepatic stellate cells in liver disease. J Gastroenterol Hepatol. 27(Suppl 2): S75–S79. 2012. View Article : Google Scholar | |
|
Rippe RA and Brenner DA: From quiescence to activation: Gene regulation in hepatic stellate cells. Gastroenterology. 127:1260–1262. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW and Mann DA: Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: Implications for wound healing and fibrogenesis. Cell Death Differ. 14:275–285. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Tsukamoto H, She H, Hazra S, Cheng J and Miyahara T: Anti-adipogenic regulation underlies hepatic stellate cell transdifferentiation. J Gastroenterol Hepatol. 21(Suppl 3): S102–S105. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Elpek GÖ: Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update. World J Gastroenterol. 20:7260–7276. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Fausther M, Lavoie EG and Dranoff JA: Contribution of Myofibroblasts of Different Origins to Liver Fibrosis. Curr Pathobiol Rep. 1:225–230. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bosselut N, Housset C, Marcelo P, Rey C, Burmester T, Vinh J, Vaubourdolle M, Cadoret A and Baudin B: Distinct proteomic features of two fibrogenic liver cell populations: Hepatic stellate cells and portal myofibroblasts. Proteomics. 10:1017–1028. 2010.PubMed/NCBI | |
|
Dranoff JA and Wells RG: Portal fibroblasts: Underappreciated mediators of biliary fibrosis. Hepatology. 51:1438–1444. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Uchio K, Tuchweber B, Manabe N, Gabbiani G, Rosenbaum J and Desmoulière A: Cellular retinol-binding protein-1 expression and modulation during in vivo and in vitro myofibroblastic differentiation of rat hepatic stellate cells and portal fibroblasts. Lab Invest. 82:619–628. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Iwaisako K, Brenner DA and Kisseleva T: What's new in liver fibrosis? The origin of myofibroblasts in liver fibrosis. J Gastroenterol Hepatol. 27(Suppl 2): S65–S68. 2012. View Article : Google Scholar | |
|
Tuchweber B, Desmoulière A, Bochaton-Piallat ML, Rubbia-Brandt L and Gabbiani G: Proliferation and phenotypic modulation of portal fibroblasts in the early stages of cholestatic fibrosis in the rat. Lab Invest. 74:265–278. 1996.PubMed/NCBI | |
|
Kinnman N, Francoz C, Barbu V, Wendum D, Rey C, Hultcrantz R, Poupon R and Housset C: The myofibroblastic conversion of peribiliary fibrogenic cells distinct from hepatic stellate cells is stimulated by platelet-derived growth factor during liver fibrogenesis. Lab Invest. 83:163–173. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Quan TE, Cowper S, Wu SP, Bockenstedt LK and Bucala R: Circulating fibrocytes: Collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol. 36:598–606. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Strieter RM, Keeley EC, Burdick MD and Mehrad B: The role of circulating mesenchymal progenitor cells, fibrocytes, in promoting pulmonary fibrosis. Trans Am Clin Climatol Assoc. 120:49–59. 2009.PubMed/NCBI | |
|
Kisseleva T, Uchinami H, Feirt N, Quintana-Bustamante O, Segovia JC, Schwabe RF and Brenner DA: Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J Hepatol. 45:429–438. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Kisseleva T and Brenner DA: The phenotypic fate and functional role for bone marrow-derived stem cells in liver fibrosis. J Hepatol. 56:965–972. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Forbes SJ and Parola M: Liver fibrogenic cells. Best Pract Res Clin Gastroenterol. 25:207–217. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H and Kalluri R: Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem. 282:23337–23347. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Milani S, Herbst H, Schuppan D, Stein H and Surrenti C: Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease. Am J Pathol. 139:1221–1229. 1991.PubMed/NCBI | |
|
Pinzani M, Milani S, Herbst H, DeFranco R, Grappone C, Gentilini A, Caligiuri A, Pellegrini G, Ngo DV, Romanelli RG and Gentilini P: Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am J Pathol. 148:785–800. 1996.PubMed/NCBI | |
|
Omenetti A, Porrello A, Jung Y, Yang L, Popov Y, Choi SS, Witek RP, Alpini G, Venter J and Vandongen HM: Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. J Clin Invest. 118:3331–3342. 2008.PubMed/NCBI | |
|
Xia JL, Dai C, Michalopoulos GK and Liu Y: Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation. Am J Pathol. 168:1500–1512. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Hay ED: An overview of epithelio-mesenchymal transformation. Acta Anat (Basel). 154:8–20. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Zeisberg M and Neilson EG: Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 119:1429–1437. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE and Neilson EG: Identification and characterization of a fibroblast marker: FSP1. J Cell Biol. 130:393–405. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Okada H, Danoff TM, Kalluri R and Neilson EG: Early role of Fsp1 in epithelial-mesenchymal transformation. Am J Physiol. 273:F563–F574. 1997.PubMed/NCBI | |
|
Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F and Kalluri R: BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med. 9:964–968. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Lee HY, Jeon HS, Song EK, Han MK, Park SI, Lee SI, Yun HJ, Kim JR, Kim JS, Lee YC, et al: CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL-mediated osteoclastogenesis: Evidence of NF-kappaB-dependent, CD40-mediated bone destruction in rheumatoid arthritis. Arthritis Rheum. 54:1747–1758. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Iwano M, Plieth D, Danoff TM, Xue C, Okada H and Neilson EG: Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest. 110:341–350. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, et al: Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 13:952–961. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Potenta S, Zeisberg E and Kalluri R: The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer. 99:1375–1379. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Li Y, Wang J and Asahina K: Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial-mesenchymal transition in liver injury. Proc Natl Acad Sci USA. 110:2324–2329. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Pagan R, Martín I, Llobera M and Vilaró S: Epithelial-mesenchymal transition of cultured rat neonatal hepatocytes is differentially regulated in response to epidermal growth factor and dimethyl sulfoxide. Hepatology. 25:598–606. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Valdés F, Alvarez AM, Locascio A, Vega S, Herrera B, Fernández M, Benito M, Nieto MA and Fabregat I: The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor beta in fetal rat hepatocytes. Mol Cancer Res. 1:68–78. 2002.PubMed/NCBI | |
|
Sicklick JK, Choi SS, Bustamante M, McCall SJ, Pérez EH, Huang J, Li YX, Rojkind M and Diehl AM: Evidence for epithelial-mesenchymal transitions in adult liver cells. Am J Physiol Gastrointest Liver Physiol. 291:G575–G583. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Xue ZF, Wu XM and Liu M: Hepatic regeneration and the epithelial to mesenchymal transition. World J Gastroenterol. 19:1380–1386. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Yang J and Liu Y: Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. J Am Soc Nephrol. 13:96–107. 2002.PubMed/NCBI | |
|
Eghbali-Fatourechi G, Sieck GC, Prakash YS, Maercklein P, Gores GJ and Fitzpatrick LA: Type I procollagen production and cell proliferation is mediated by transforming growth factor-beta in a model of hepatic fibrosis. Endocrinology. 137:1894–1903. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Hay ED and Zuk A: Transformations between epithelium and mesenchyme: Normal, pathological and experimentally induced. Am J Kidney Dis. 26:678–690. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Witzgall R, Brown D, Schwarz C and Bonventre JV: Localization of proliferating cell nuclear antigen, vimentin, c-Fos and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments and a large pool of mitotically active and dedifferentiated cells. J Clin Invest. 93:2175–2188. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Klass BR, Grobbelaar AO and Rolfe KJ: Transforming growth factor beta1 signalling, wound healing and repair: A multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J. 85:9–14. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Martin M, Lefaix J and Delanian S: TGF-beta1 and radiation fibrosis: A master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys. 47:277–290. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Del Castillo G, Murillo MM, Alvarez-Barrientos A, Bertran E, Fernández M, Sánchez A and Fabregat I: Autocrine production of TGF-beta confers resistance to apoptosis after an epithelial-mesenchymal transition process in hepatocytes: Role of EGF receptor ligands. Exp Cell Res. 312:2860–2871. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL and Arteaga CL: Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem. 275:36803–36810. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Cicchini C, Laudadio I, Citarella F, Corazzari M, Steindler C, Conigliaro A, Fantoni A, Amicone L and Tripodi M: TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling. Exp Cell Res. 314:143–152. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Bhowmick NA, Zent R, Ghiassi M, McDonnell M and Moses HL: Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J Biol Chem. 276:46707–46713. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Xie L, Law BK, Chytil AM, Brown KA, Aakre ME and Moses HL: Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia. 6:603–610. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang H, Liu L, Wang Y, Zhao G, Xie R, Liu C, Xiao X, Wu K, Nie Y, Zhang H and Fan D: KLF8 involves in TGF-beta-induced EMT and promotes invasion and migration in gastric cancer cells. J Cancer Res Clin Oncol. 139:1033–1042. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Porsch H, Bernert B, Mehić M, Theocharis AD, Heldin CH and Heldin P: Efficient TGFβ-induced epithelial-mesenchymal transition depends on hyaluronan synthase HAS2. Oncogene. 32:4355–4365. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Ding X, Park SI, McCauley LK and Wang CY: Signaling between transforming growth factor β (TGF-β) and transcription factor SNAI2 represses expression of microRNA miR-203 to promote epithelial-mesenchymal transition and tumor metastasis. J Biol Chem. 288:10241–10253. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kim KH, Lee WR, Kang YN, Chang YC and Park KW: Inhibitory effect of nuclear factor-κB decoy oligodeoxynucleotide on liver fibrosis through regulation of the epithelial-mesenchymal transition. Hum Gene Ther. 25:721–729. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Leask A and Abraham DJ: TGF-beta signaling and the fibrotic response. FASEB J. 18:816–827. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Zavadil J, Cermak L, Soto-Nieves N and Böttinger EP: Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 23:1155–1165. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Park JH, Yoon J, Lee KY and Park B: Effects of geniposide on hepatocytes undergoing epithelial-mesenchymal transition in hepatic fibrosis by targeting TGFβ/Smad and ERK-MAPK signaling pathways. Biochimie. 113:26–34. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Lee WR, Kim KH, An HJ, Kim JY, Lee SJ, Han SM, Pak SC and Park KK: Apamin inhibits hepatic fibrosis through suppression of transforming growth factor β1-induced hepatocyte epithelial-mesenchymal transition. Biochem Biophys Res Commun. 450:195–201. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Wang S, Lee Y, Kim J, Hyun J, Lee K, Kim Y and Jung Y: Potential role of Hedgehog pathway in liver response to radiation. PLoS One. 8:e741412013. View Article : Google Scholar : PubMed/NCBI | |
|
Ingham PW and McMahon AP: Hedgehog signaling in animal development: Paradigms and principles. Genes Dev. 15:3059–3087. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
van den Brink GR: Hedgehog signaling in development and homeostasis of the gastrointestinal tract. Physiol Rev. 87:1343–1375. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Varjosalo M and Taipale J: Hedgehog: Functions and mechanisms. Genes Dev. 22:2454–2472. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Kahila Bar-Gal G, Kim MJ, Klein A, Shin DH, Oh CS, Kim JW, Kim TH, Kim SB, Grant PR, Pappo O, et al: Tracing hepatitis B virus to the 16th century in a Korean mummy. Hepatology. 56:1671–1680. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Choi SS, Omenetti A, Witek RP, Moylan CA, Syn WK, Jung Y, Yang L, Sudan DL, Sicklick JK, Michelotti GA, et al: Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis. Am J Physiol Gastrointest Liver Physiol. 297:G1093–G1106. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Kaimori A, Potter J, Kaimori JY, Wang C, Mezey E and Koteish A: Transforming growth factor-beta1 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro. J Biol Chem. 282:22089–22101. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Taura K, Miura K, Iwaisako K, Osterreicher CH, Kodama Y, Penz-Osterreicher M and Brenner DA: Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice. Hepatology. 51:1027–1036. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SJ, Kim KH and Park KK: Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition. World J Hepatol. 6:207–216. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Scholten D, Osterreicher CH, Scholten A, Iwaisako K, Gu G, Brenner DA and Kisseleva T: Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. Gastroenterology. 139:987–998. 2010. View Article : Google Scholar : PubMed/NCBI |
