Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Biomed Pharmacother. 2017 Jan;85:575-581. doi: 10.1016/j.biopha.2016.11.066. Epub 2016 Nov 24.
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-β1-treated HSCs. Knockdown of HIPK2 significantly inhibited TGF-β1-induced HSCs proliferation, as well as decreased the expression levels of α-SMA and collagen I. Furthermore, knockdown of HIPK2 attenuated the phosphorylation of Smad3 in the presence of TGF-β1. In conclusion, these results demonstrated that HIPK2 may function as a novel regulator to modulate HSC activation, potentially by inhibiting the TGF-β1/Smad3 signaling pathway. The results provide supporting evidence that HIPK2 may be a potential target for the treatment of liver fibrosis.
同源结构域相互作用蛋白激酶 2（HIPK2）是 HIPK 家族的一员，被认为是纤维化过程中的关键调节因子。然而，HIPK2 在肝星状细胞（HSCs）活化和肝纤维化中的作用尚不清楚。因此，在本研究中，我们研究了 HIPK2 在 HSCs 活化和肝纤维化中的作用。我们的结果表明，HIPK2 的表达在肝纤维化组织和 TGF-β1 处理的 HSCs 中显著上调。HIPK2 的敲低显著抑制了 TGF-β1 诱导的 HSCs 增殖，并降低了α-SMA 和胶原 I 的表达水平。此外，在 TGF-β1 存在的情况下，HIPK2 的敲低减弱了 Smad3 的磷酸化。总之，这些结果表明 HIPK2 可能作为一种新的调节因子，通过抑制 TGF-β1/Smad3 信号通路来调节 HSC 活化。这些结果为 HIPK2 可能成为治疗肝纤维化的潜在靶点提供了证据。
