【摘要】：目的研究蛋白激酶C結(jié)合蛋白1(PICK1)在小鼠肝纖維及活化的肝星狀細(xì)胞中的表達(dá)變化,并探討其對(duì)人肝星狀細(xì)胞株(LX-2)活化的影響。方法建立四氯化碳(CCl4)誘導(dǎo)的小鼠肝纖維化模型,觀察PICK1在肝纖維化過(guò)程中的表達(dá)變化;轉(zhuǎn)化生長(zhǎng)因子β1(TGF-β1)刺激LX-2活化,Western blot測(cè)定PICK1的蛋白表達(dá)情況;轉(zhuǎn)染PICK1過(guò)表達(dá)質(zhì)粒至LX-2中,再以TGF-β1誘導(dǎo)活化,Western blot檢測(cè)PICK1、α平滑肌肌動(dòng)蛋白(α-SMA)、I型膠原(Col1a1)和Smad2、3及其磷酸化水平的蛋白表達(dá)情況。結(jié)果正常組小鼠肝臟中PICK1表達(dá)較高,隨著肝纖維化的加重,PICK1的表達(dá)逐漸遞減。TGF-β1誘導(dǎo)活化的LX-2細(xì)胞中PICK1表達(dá)降低。轉(zhuǎn)染PICK1過(guò)表達(dá)質(zhì)粒后,TGF-β1誘導(dǎo)的α-SMA、Colla1的表達(dá)明顯減少,且Smad2、3磷酸化水平顯著下降。結(jié)論 PICK1在纖維化肝組織及活化的HSC中表達(dá)下調(diào)。過(guò)表達(dá)PICK1可抑制TGF-β1誘導(dǎo)的LX-2活化,可能是通過(guò)抑制TGF-β/Smad通路而發(fā)揮作用,為肝纖維化的防治研究提供了新的思路和靶點(diǎn)。
[Abstract]:Objective to investigate the expression of protein kinase C binding protein 1 (PICK1) in mouse hepatic fibers and activated hepatic stellate cells (HSCs) and to investigate the effect of protein kinase C binding protein 1 (PICK1) on the activation of human hepatic stellate cell line (LX-2). Methods the liver fibrosis model of mice induced by carbon tetrachloride (CCl4) was established to observe the expression of PICK1 during hepatic fibrosis, the expression of PICK1 protein was detected by LX-2 activation blot stimulated by transforming growth factor 尾 1 (TGF- 尾 1), and the overexpression plasmid of PICK1 was transfected into LX-2. The expression of PICK1, 偽 smooth muscle actin (偽 -SMA) type I collagen (Col1a1) and Smad2,3 and their phosphorylation levels were detected by TGF- 尾 1-induced activation Western blot. Results the expression of PICK1 in the liver of normal mice was higher, and the expression of PICK1 decreased gradually with the exacerbation of hepatic fibrosis. The expression of PICK1 in activated LX-2 cells induced by TGF- 尾 1 decreased. The expression of 偽 -SMA-Colla1 induced by TGF- 尾 1 was significantly decreased and the phosphorylation level of Smad2,3 was significantly decreased after transfection of PICK1 overexpression plasmid. Conclusion the expression of PICK1 is down-regulated in fibrotic liver tissue and activated HSC. Overexpression of PICK1 can inhibit the LX-2 activation induced by TGF- 尾 1, which may play a role by inhibiting the TGF- 尾 / Smad pathway, which provides a new idea and target for the prevention and treatment of hepatic fibrosis.
【作者單位】： 安徽醫(yī)科大學(xué)藥學(xué)院;安徽醫(yī)科大學(xué)肝病研究所;安徽醫(yī)科大學(xué)安徽省創(chuàng)新藥物產(chǎn)業(yè)共性研究院;
【基金】：國(guó)家自然科學(xué)基金(編號(hào):81273526、81473268) 安徽省重點(diǎn)科技攻關(guān)項(xiàng)目(編號(hào):1301042212) 安徽省自然科學(xué)基金(編號(hào):1308085MH145) 高等學(xué)校博士學(xué)科點(diǎn)專(zhuān)項(xiàng)科研基金(編號(hào):20123420120001)
【分類(lèi)號(hào)】：R575.2

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本文編號(hào)：2203622