Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Biomed Pharmacother. 2017 May;89:1387-1391. doi: 10.1016/j.biopha.2017.03.021. Epub 2017 Mar 19.
Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells. Furthermore, CTRP3 overexpression greatly inhibited the expression level of phosphorylation of Smad3 in TGF-β1-stimulated HSC-T6 cells. In conclusion, the present study demonstrated that CTRP3 inhibited the proliferation and migration of TGF-β1-induced HSC-T6 cells and attenuated liver fibrosis, at least in part, through inhibiting the Smad signaling pathway. These findings suggest that CTRP3 may be a promising therapeutic target for the treatment of liver fibrosis.
肝星状细胞（HSCs）的激活在肝纤维化的发展中起着关键作用。C1q/肿瘤坏死因子相关蛋白 3（CTRP3）是 CTRPs 家族的一员，参与纤维化。然而，关于 CTRP3 在肝纤维化中的作用知之甚少。本研究旨在确定其在肝纤维化中的作用，并探讨可能的机制。我们的结果表明，CTRP3 在肝纤维化组织和激活的 HSCs 中低表达。CTRP3 的过表达抑制了 HSCs 的增殖和迁移，并抑制了转化生长因子-β1（TGF-β1）刺激的 HSC-T6 细胞中细胞外基质（ECM）的表达。此外，CTRP3 的过表达极大地抑制了 TGF-β1 刺激的 HSC-T6 细胞中 Smad3 磷酸化的表达水平。总之，本研究表明，CTRP3 通过抑制 Smad 信号通路抑制 TGF-β1 诱导的 HSC-T6 细胞的增殖和迁移，并减轻肝纤维化，至少部分如此。这些发现表明，CTRP3 可能是治疗肝纤维化的有前途的治疗靶点。
