As an outcome of chronic liver disease, liver fibrosis involves the activation of hepatic stellate cells (HSCs) caused by a variety of chronic liver injuries. It is important to explore approaches to inhibit the activation and proliferation of HSCs for the treatment of liver fibrosis. PLK1 is overexpressed in many human tumour cells and has become a popular drug target in tumour therapy. Therefore, further study of the function of PLK1 in the cell cycle is valid. In the present study, we found that PLK1 expression was elevated in primary HSCs isolated from CCl₄‐induced liver fibrosis mice and LX‐2 cells stimulated with TGF‐β1. Knockdown of PLK1 inhibited α‐SMA and Col1α1 expression and reduced the activation of HSCs in CCl₄‐induced liver fibrosis mice and LX‐2 cells stimulated with TGF‐β1. We further showed that inhibiting the expression of PLK1 reduced the proliferation of HSCs and promoted HSCs apoptosis in vivo and in vitro. Furthermore, we found that the Wnt/β‐catenin signalling pathway may be essential for PLK1‐mediated HSCs activation. Together, blocking PLK1 effectively suppressed liver fibrosis by inhibiting HSC activation, which may provide a new treatment strategy for liver fibrosis.

中文翻译：

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PLK1通过Wnt /β-catenin信号传导途径调节肝星状细胞的活化和肝纤维化。

作为慢性肝病的结果，肝纤维化涉及各种慢性肝损伤引起的肝星状细胞（HSC）的激活。重要的是探索抑制HSCs活化和增殖的方法，以治疗肝纤维化。PLK1在许多人类肿瘤细胞中过表达，并已成为肿瘤治疗中流行的药物靶标。因此，进一步研究PLK1在细胞周期中的功能是有效的。在本研究中，我们发现从CCl ₄诱导的肝纤维化小鼠和TGF-β1刺激的LX-2细胞分离的原代HSC中，PLK1表达升高。敲低PLK1抑制α-SMA和Col1α1表达并减少CCl ₄中HSC的活化TGF-β1刺激的肝纤维化小鼠和LX-2细胞。我们进一步表明，抑制PLK1的表达降低了体内和体外HSC的增殖并促进了HSC的凋亡。此外，我们发现Wnt /β-catenin信号通路可能对PLK1介导的HSC激活至关重要。总之，阻断PLK1可通过抑制HSC激活有效抑制肝纤维化，这可能为肝纤维化提供新的治疗策略。