caa a22 4500 606236457 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2258-1 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2258-1 Smad2 protects against TGF-β1/Smad3-mediated collagen synthesis in human hepatic stellate cells during hepatic fibrosis [Elektronische Daten] [Lei Zhang, Changwei Liu, Xiao-ming Meng, Cheng Huang, Fengyun Xu, Jun Li] With structural similaritybut functional diversity, Smad2 and Smad3 interact with each other to mediate transforming growth factor-β (TGF-β)-triggered signaling transduction. However, in the hepatic fibrosis, the detailed roles of R-Smads, and interaction between Smad2 and Smad3 are still undefined. In this setting, we established a rat model of CCl4-induced hepatic fibrosis in vivo and TGF-β1-treated hepatic stellate cell model in vitro to detect whether Smad2 and Smad3 play distinct roles in mediating liver fibrogenesis. Results indicated that both phosphorylation of Smad2 and Smad3 were detected in the hepatic stellate cells of liver fibrotic tissues and cells. Furthermore, In vitro data demonstrated that knockdown of Smad2 in human hepatic stellate cells increased expression of collagen I (Col.I), tissue inhibitor of metalloproteinase-1 (TIMP-1) whereas decreasing expression of the matrix metalloproteinases-2(MMP-2) in presence of TGF-β1 compared with control group. In contrast, knockdown of Smad3 significantly reduced TGF-β1-induced Col.I production. These findings were further evident by the results that overexpression of Smad2 attenuated the expression of Col.I and TIMP-1, but enhanced MMP-2 whereas overexpression of Smad3 showed the opposite effect. Furthermore, Smad2 suppressed the phosphorylation and nuclear translocation of Smad3, which may protect against Smad3-mediated fibrotic response. Collectively, Smad2 may be a potential therapeutic target for the treatment of hepatic fibrosis. Springer Science+Business Media New York, 2014 Hepatic fibrosis nationallicence TGF-β1 nationallicence Smad2 nationallicence Smad3 nationallicence TGF-β1 : Transforming growth factor-β1 nationallicence TIMP-1 : Issue inhibitor of metalloproteinase 1 nationallicence MMP-2 : Matrix-degrading enzyme 2 nationallicence EMT : Epithelial-to-mesenchymal transition nationallicence ECM : Extracellular matrix nationallicence KO : Knockout nationallicence SMAD2 : Mothers against decapentaplegic homolog 2 nationallicence SMAD3 : Mothers against decapentaplegic homolog 3 nationallicence Zhang Lei School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut Liu Changwei School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut Meng Xiao-ming School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut Huang Cheng School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut Xu Fengyun School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut Li Jun School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 17-28 0300-8177 400:1-2<17 2015 400 11010 https://doi.org/10.1007/s11010-014-2258-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2258-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Lei School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut NATIONALLICENCE 700 1- Liu Changwei School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut NATIONALLICENCE 700 1- Meng Xiao-ming School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut NATIONALLICENCE 700 1- Huang Cheng School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut NATIONALLICENCE 700 1- Xu Fengyun School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut NATIONALLICENCE 700 1- Li Jun School of Pharmacy, Anhui Medical University, 230032, Hefei, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 17-28 0300-8177 400:1-2<17 2015 400 11010