Excellence in Research and Innovation for Humanity

International Science Index


Select areas to restrict search in scientific publication database:
10006259
MiR-200a/ZEB1 Pathway in Liver Fibrogenesis of Biliary Atresia
Abstract:
Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and α-SMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA.

References:

[1] Hartley J, Harnden A, Kelly D. Biliary atresia. BMJ 2010; 340: c2383.
[2] Kasai M. Advances in treatment of biliary atresia. Jpn J Surg 1983; 13(4): 265-276.
[3] Pakarinen MP, Rintala RJ. Surgery of biliary atresia. Scand J Surg 2011; 100(1): 49-53.
[4] Yang LY, Fu J, Peng XF, Pang SY, Gao KK, Chen ZR, He LJ, Wen Z, Wang H, Li L, Wang FH, Yu JK, Xu Y, Gong ST, Xia HM, Liu HY. Validation of aspartate aminotransferase to platelet ratio for diagnosis of liver fibrosis and prediction of postoperative prognosis in infants with biliary atresia. World J Gastroenterol 2015; 21(19): 5893-5900.
[5] Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136(2): 215-233.
[6] Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 2010; 9(10): 775-789.
[7] Yang S, Banerjee S, de Freitas A, Sanders YY, Ding Q, Matalon S, Thannickal VJ, Abraham E, Liu G. Participation of miR-200 in pulmonary fibrosis. Am J Pathol 2012; 180(2): 484-493.
[8] Xiong M, Jiang L, Zhou Y, Qiu W, Fang L, Tan R, Wen P, Yang J. The miR-200 family regulates TGF-beta1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression. Am J Physiol Renal Physiol 2012; 302(3): F369-F379.
[9] Choi SS, Diehl AM. Epithelial-to-mesenchymal transitions in the liver. Hepatology 2009; 50(6): 2007-2013.
[10] Sicklick JK, Choi SS, Bustamante M, McCall SJ, Perez EH, Huang J, Li YX, Rojkind M, Diehl AM. Evidence for epithelial-mesenchymal transitions in adult liver cells. Am J Physiol Gastrointest Liver Physiol 2006; 291(4): G575-G583.
[11] Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18(10): 997-1006.
[12] Zahm AM, Hand NJ, Boateng LA, Friedman JR. Circulating microRNA is a biomarker of biliary atresia. J Pediatr Gastroenterol Nutr 2012; 55(4): 366-369.
[13] Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet 2009; 374(9702): 1704-1713.
[14] Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, Et A. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22(6): 696-699.
[15] Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Tomokuni A, Takemasa I, Umeshita K, Kanto T, Doki Y, Mori M. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol 2012; 56(1): 167-175.
[16] Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008; 105(30): 10513-10518.
[17] Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, Jandeleit-Dahm K, Burns WC, Thomas MC, Cooper ME, Kantharidis P. miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes 2011; 60(1): 280-287.
[18] Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, Kosaka N, Ochiya T, Shimotohno K. The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families. PLoS One 2011; 6(1): e16081.
[19] Xiao Y, Wang J, Yan W, Zhou Y, Chen Y, Zhou K, Wen J, Wang Y, Cai W. Dysregulated miR-124 and miR-200 expression contribute to cholangiocyte proliferation in the cholestatic liver by targeting IL-6/STAT3 signalling. J Hepatol 2015; 62(4): 889-896.
[20] Diaz R, Kim JW, Hui JJ, Li Z, Swain GP, Fong KS, Csiszar K, Russo PA, Rand EB, Furth EE, Wells RG. Evidence for the epithelial to mesenchymal transition in biliary atresia fibrosis. Hum Pathol 2008; 39(1): 102-115.
[21] Deng YH, Pu CL, Li YC, Zhu J, Xiang C, Zhang MM, Guo CB. Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia. Dig Dis Sci 2011; 56(3): 731-740.
[22] Harada K, Sato Y, Ikeda H, Isse K, Ozaki S, Enomae M, Ohama K, Katayanagi K, Kurumaya H, Matsui A, Nakanuma Y. Epithelial-mesenchymal transition induced by biliary innate immunity contributes to the sclerosing cholangiopathy of biliary atresia. J Pathol 2009; 217(5): 654-664.
[23] Cong N, Du P, Zhang A, Shen F, Su J, Pu P, Wang T, Zjang J, Kang C, Zhang Q. Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/beta-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncol Rep 2013; 29(4): 1579-1587.
[24] Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 2009; 119(6): 1417-1419.
[25] Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest 2009; 119(6): 1429-1437.
[26] Kisseleva T, Cong M, Paik Y, Scholten D, Jiang C, Benner C, Iwaisako K, Moore-Morris T, Scott B, Tsukamoto H, Evans SM, Dillmann W, Glass CK, Brenner DA. Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis. Proc Natl Acad Sci U S A 2012; 109(24): 9448-9453.
[27] Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res 2008; 68(19): 7846-7854.
[28] Dong R, Luo Y, Zheng S. alpha-SMA overexpression associated with increased liver fibrosis in infants with biliary atresia. J Pediatr Gastroenterol Nutr 2012; 55(6): 653-656.
[29] Suominen JS, Lampela H, Heikkila P, Lohi J, Jalanko H, Pakarinen MP. Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia. World J Gastroenterol 2014; 20(12): 3312-3319.
[30] Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H, Kalluri R. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 2007; 282(32): 23337-23347.
[31] Xiao Y, Zhou Y, Chen Y, Zhou K, Wen J, Wang Y, Wang J, Cai W. The expression of epithelial-mesenchymal transition-related proteins in biliary epithelial cells is associated with liver fibrosis in biliary atresia. Pediatr Res 2015; 77(2): 310-315.
[32] Dai W, Zhao J, Tang N, Zeng X, Wu K, Ye C, Shi J, Lu C, Ning B, Zhang J, Lin Y. MicroRNA-155 attenuates activation of hepatic stellate cell by simultaneously preventing EMT process and ERK1 signalling pathway. Liver Int 2015; 35(4): 1234-1243.
Vol:11 No:09 2017Vol:11 No:08 2017Vol:11 No:07 2017Vol:11 No:06 2017Vol:11 No:05 2017Vol:11 No:04 2017Vol:11 No:03 2017Vol:11 No:02 2017Vol:11 No:01 2017
Vol:10 No:12 2016Vol:10 No:11 2016Vol:10 No:10 2016Vol:10 No:09 2016Vol:10 No:08 2016Vol:10 No:07 2016Vol:10 No:06 2016Vol:10 No:05 2016Vol:10 No:04 2016Vol:10 No:03 2016Vol:10 No:02 2016Vol:10 No:01 2016
Vol:9 No:12 2015Vol:9 No:11 2015Vol:9 No:10 2015Vol:9 No:09 2015Vol:9 No:08 2015Vol:9 No:07 2015Vol:9 No:06 2015Vol:9 No:05 2015Vol:9 No:04 2015Vol:9 No:03 2015Vol:9 No:02 2015Vol:9 No:01 2015
Vol:8 No:12 2014Vol:8 No:11 2014Vol:8 No:10 2014Vol:8 No:09 2014Vol:8 No:08 2014Vol:8 No:07 2014Vol:8 No:06 2014Vol:8 No:05 2014Vol:8 No:04 2014Vol:8 No:03 2014Vol:8 No:02 2014Vol:8 No:01 2014
Vol:7 No:12 2013Vol:7 No:11 2013Vol:7 No:10 2013Vol:7 No:09 2013Vol:7 No:08 2013Vol:7 No:07 2013Vol:7 No:06 2013Vol:7 No:05 2013Vol:7 No:04 2013Vol:7 No:03 2013Vol:7 No:02 2013Vol:7 No:01 2013
Vol:6 No:12 2012Vol:6 No:11 2012Vol:6 No:10 2012Vol:6 No:09 2012Vol:6 No:08 2012Vol:6 No:07 2012Vol:6 No:06 2012Vol:6 No:05 2012Vol:6 No:04 2012Vol:6 No:03 2012Vol:6 No:02 2012Vol:6 No:01 2012
Vol:5 No:12 2011Vol:5 No:11 2011Vol:5 No:10 2011Vol:5 No:09 2011Vol:5 No:08 2011Vol:5 No:07 2011Vol:5 No:06 2011Vol:5 No:05 2011Vol:5 No:04 2011Vol:5 No:03 2011Vol:5 No:02 2011Vol:5 No:01 2011
Vol:4 No:12 2010Vol:4 No:11 2010Vol:4 No:10 2010Vol:4 No:09 2010Vol:4 No:08 2010Vol:4 No:07 2010Vol:4 No:06 2010Vol:4 No:05 2010Vol:4 No:04 2010Vol:4 No:03 2010Vol:4 No:02 2010Vol:4 No:01 2010
Vol:3 No:12 2009Vol:3 No:11 2009Vol:3 No:10 2009Vol:3 No:09 2009Vol:3 No:08 2009Vol:3 No:07 2009Vol:3 No:06 2009Vol:3 No:05 2009Vol:3 No:04 2009Vol:3 No:03 2009Vol:3 No:02 2009Vol:3 No:01 2009
Vol:2 No:12 2008Vol:2 No:11 2008Vol:2 No:10 2008Vol:2 No:09 2008Vol:2 No:08 2008Vol:2 No:07 2008Vol:2 No:06 2008Vol:2 No:05 2008Vol:2 No:04 2008Vol:2 No:03 2008Vol:2 No:02 2008Vol:2 No:01 2008
Vol:1 No:12 2007Vol:1 No:11 2007Vol:1 No:10 2007Vol:1 No:09 2007Vol:1 No:08 2007Vol:1 No:07 2007Vol:1 No:06 2007Vol:1 No:05 2007Vol:1 No:04 2007Vol:1 No:03 2007Vol:1 No:02 2007Vol:1 No:01 2007