配对相关同源盒蛋白1调节血小板衍生生长因子诱导的肝星状细胞在肝纤维化中的趋化作用。
Paired related homeobox protein 1 regulates PDGF-induced chemotaxis of hepatic stellate cells in liver fibrosis.
作者信息
Gong Jin, Han Jian, He Jiayi, Liu Jingmei, Han Ping, Wang Yunwu, Li Mengke, Li Dongxiao, Ding Xiangming, Du Zhipeng, Liao Jiazhi, Tian Dean
机构信息
Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Lab Invest. 2017 Sep;97(9):1020-1032. doi: 10.1038/labinvest.2017.65. Epub 2017 Jul 24.
Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFβR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways. In vivo, an adenoviral-mediated Prrx1 shRNA administration attenuated liver fibrosis in thioacetamide-induced fibrotic models. These studies reveal a role of Prrx1 as a modulator of PDGF-dependent signaling in HSCs, and inhibiting its expression may offer a therapeutic approach for hepatic fibrosis.
血小板衍生生长因子（PDGF）/PDGFβ受体（PDGFβR）轴的激活在肝纤维化中起关键作用。然而，调节PDGF信号传导的机制尚待阐明。本研究表明，配对相关同源盒蛋白1（Prrx1）通过调节金属蛋白酶MMP2和MMP9的表达参与PDGF依赖性肝星状细胞（HSC）迁移。PDGF通过激活ERK/Sp1和PI3K/Akt/Ets1途径提高Prrx1水平。在体内，腺病毒介导的Prrx1 shRNA给药减轻了硫代乙酰胺诱导的纤维化模型中的肝纤维化。这些研究揭示了Prrx1作为HSC中PDGF依赖性信号调节剂的作用，抑制其表达可能为肝纤维化提供一种治疗方法。
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