Knockdown of HIPK2 attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1

被引：14
|
作者：
He, Ping [1 ]
Yu, Zu-jiang [1 ]
Sun, Chang-yu [1 ]
Jiao, Shu-jie [2 ]
Jiang, He-qing [1 ]
机构：
[1] Zhengzhou Univ, Dept Infect Dis, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China
[2] Zhengzhou Univ, Dept Neurol, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China
来源：
BIOMEDICINE & PHARMACOTHERAPY | 2017年 / 85卷
关键词：
Liver fibrosis; Homeodomain-interacting protein kinase 2 (HIPK2); Hepatic stellate cells (HSCs); TGF-beta 1/Smad pathway; LIVER FIBROSIS; EXTRACELLULAR-MATRIX; SIGNALING PATHWAY; TGF-BETA; EXPRESSION; PROTEIN; ACTIVATION; COLLAGEN; SMAD3; PROLIFERATION;
D O I：
10.1016/j.biopha.2016.11.066
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Homeodomain-interacting protein kinase 2 (HIPK2), a member of HIPKs family, is considered as a key regulator in fibrosis. However, the roles of HIPK2 in hepatic stellate cells (HSCs) activation and liver fibrosis are still unclear. Therefore, in this study, we investigated the roles of HIPK2 in HSCs activation and liver fibrosis. Our results showed that HIPK2 expression was significantly up-regulated in liver fibrotic tissues and TGF-b1-treated HSCs. Knockdown of HIPK2 significantly inhibited TGF-beta 1-induced HSCs proliferation, as well as decreased the expression levels of alpha-SMA and collagen I. Furthermore, knockdown of HIPK2 attenuated the phosphorylation of Smad3 in the presence of TGF-beta 1. In conclusion, these results demonstrated that HIPK2 may function as a novel regulator to modulate HSC activation, potentially by inhibiting the TGF-beta 1/Smad3 signaling pathway. The results provide supporting evidence that HIPK2 may be a potential target for the treatment of liver fibrosis. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：575 / 581
页数：7
相关论文
共 50 条
  • [31] IL-17A AND IL-17F ACTIVATES PRO-FIBROGENIC SIGNALS IN KUPFFER CELLS AND HEPATIC STELLATE CELL
    Meng, Fanli
    Kisseleva, Tatiana
    Seki, Ekihiro
    Scholten, David
    Paik, Yonghan
    Wang, Kai
    Brenner, David A.
    HEPATOLOGY, 2009, 50 (04) : 826A - 827A
  • [32] HCV INFECTION PROMOTES CYTOSKELETAL REORGANIZATION IN HEPATOCYTES AND A PRO-FIBROGENIC PHENOTYPE IN HEPATIC STELLATE CELLS BY THE ACTIVATION OF FOCAL ADHESION KINASE
    Alisi, A.
    Arciello, M.
    Petrini, S.
    Conti, B.
    Balsano, C.
    JOURNAL OF HEPATOLOGY, 2011, 54 : S409 - S409
  • [33] Effects of rhDecorin on TGF-β1 induced human hepatic stellate cells LX-2 activation
    Shi, Yue-Feng
    Zhang, Qi
    Cheung, Pik-Yuen
    Shi, Lin
    Fong, Chi-Chun
    Zhang, Yaou
    Tzang, Chi-Hung
    Chan, Bernard P. L.
    Fong, Wang-Fun
    Chun, Jay
    Kung, Hsiang-fu
    Yang, Mengsu
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2006, 1760 (11): : 1587 - 1595
  • [34] Effects of neferine on TGF-β1 induced proliferation and gremlin expression in hepatic stellate cells
    Li, Xiaofei
    Lou, Lianqing
    Wu, Shuang
    Chen, Yongxin
    Jin, Lingzhen
    BANGLADESH JOURNAL OF PHARMACOLOGY, 2012, 7 (03) : 169 - 172
  • [35] Knockdown of Fstl1 attenuates hepatic stellate cell activation through the TGF-β1/Smad3 signaling pathway
    Shang, Hongye
    Liu, Xiangjin
    Guo, Hui
    MOLECULAR MEDICINE REPORTS, 2017, 16 (05) : 7119 - 7123
  • [36] Knockdown of LOXL1 inhibits TGF-β1-induced proliferation and fibrogenesis of hepatic stellate cells by inhibition of Smad2/3 phosphorylation
    Ma, Li
    Zeng, Yanli
    Wei, Junfeng
    Yang, Dongqiang
    Ding, Gangqiang
    Liu, Junping
    Shang, Jia
    Kang, Yi
    Ji, Xinying
    BIOMEDICINE & PHARMACOTHERAPY, 2018, 107 : 1728 - 1735
  • [37] Knockdown of LOXL1 inhibits TGF-β1-induced proliferation and fibrogenesis of hepatic stellate cells by inhibition of Smad2/3 phosphorylation
    Ma, L.
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2019, 49 : 225 - 225
  • [38] Hepatitis C virus modulates focal adhesion kinase promoting cytoskeletal reorganization in hepatocytes and a pro-fibrogenic phenotype in hepatic stellate cells
    Alisi, A.
    Arciello, M.
    Petrini, S.
    Conti, B.
    Balsano, C.
    DIGESTIVE AND LIVER DISEASE, 2011, 43 : S100 - S100
  • [39] Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver
    Charrier, Alyssa
    Chen, Ruju
    Chen, Li
    Kemper, Sherri
    Hattori, Takako
    Takigawa, Masaharu
    Brigstock, David R.
    SURGERY, 2014, 156 (03) : 548 - 555
  • [40] Early response of α2(I) collagen to acetaldehyde in human hepatic stellate cells is TGF-β independent
    Svegliati-Baroni, G
    Inagaki, Y
    Rincon-Sanchez, AR
    Else, C
    Saccomanno, S
    Benedetti, A
    Ramirez, F
    Rojkind, M
    HEPATOLOGY, 2005, 42 (02) : 343 - 352
12345