全反式维甲酸对TGF-β1刺激的肝星状细胞COL1α2、MMP-2、TIMP-1以及信号通路的影响

发布时间：2018-03-02 08:34

本文关键词： 全反式维甲酸肝星状细胞肝纤维化转化生长因子-β(TGF-β) COLα MMP- TIMP- Smad /　出处：《西安交通大学学报(医学版)》2017年06期 　论文类型：期刊论文

【摘要】：目的观察全反式维甲酸对大鼠肝星状细胞(HSC-T6)增殖,以及经转化生长因子-β1(TGF-β1)刺激后Ⅰ型胶原α1链蛋白基因(COL1α2)、基质金属蛋白酶2(MMP-2)、金属蛋白酶组织抑制物1(TIMP-1)及Smad 2/3的表达变化,探讨其对肝纤维化的作用及其分子机制。方法不同浓度的全反式维甲酸(0.1、1、10μmol/L)分别作用HSC-T612、24、48h,采用噻唑蓝(MTT)比色实验检测HSC-T6增殖活性;另外,经TGF-β1(5ng/mL)刺激后的HSC-T6用不同浓度全反式维甲酸干预24h后,利用逆转录酶-聚合酶链反应(RT-PCR)技术测定COL1α2、MMP-2及TIMP-1mRNA的表达,细胞免疫化学染色法检测smad2/3蛋白的表达。结果全反式维甲酸能够抑制HSC-T6的增殖,而且具有浓度依赖性(P0.05);受外源TGF-β1 5ng/mL刺激后,HSC-T6中COL1α2、MMP-2、TIMP-1 mRNA及Smad2/3蛋白表达较对照组明显增强(P0.05),而全反式维甲酸干预能够有效降低HSC-T6受TGF-β1刺激后COL1α2、MMP-2、TIMP-1mRNA及Smad2/3蛋白的表达(P0.05)。结论全反式维甲酸能够抑制HSC-T6的增殖,下调HSC-T6受TGF-β1刺激后COL1α2、MMP-2、TIMP-1mRNA的表达,并且可能通过抑制HSC-T6中TGF-β1的下游信号蛋白Smad 2/3的表达,影响TGF-β1/Smad信号通路,发挥其抗肝纤维化作用。
[Abstract]:Objective to investigate the effects of all-trans retinoic acid (ATRA) on the proliferation of rat hepatic stellate cells (HSC-T6) and the expression of type I collagen 伪 1 chain protein gene (COL1 伪 2, matrix metalloproteinase 2 MMP 2, tissue inhibitor of metalloproteinase 1 (TIMP 1) and Smad 2/3) stimulated by transforming growth factor 尾 1 (TGF- 尾 1). To investigate the effect and molecular mechanism of TRA on hepatic fibrosis, the proliferation activity of HSC-T6 was detected by MTT colorimetric assay at 10 渭 mol / L of 10 渭 mol / L all-trans retinoic acid at different concentrations for 48 h. HSC-T6 stimulated by TGF- 尾 1ng / mL was incubated with ATRA at different concentrations for 24 h. The expression of COL1 伪 2, MMP-2 and TIMP-1mRNA was measured by reverse transcriptase polymerase chain reaction (RT PCR). The expression of smad2/3 protein was detected by immunocytochemical staining. Results all trans retinoic acid could inhibit the proliferation of HSC-T6. The expression of COL1 伪 2, MMP-2, TIMP-1 and Smad2/3 protein in HSC-T6 after stimulation with TGF- 尾 15 ng / mL was significantly higher than that in the control group. All trans retinoic acid intervention could effectively reduce the expression of COL1 伪 2 2, TIMP 1 mRNA and Smad2/3 protein in HSC-T6 stimulated by TGF- 尾 1 (P 0 05). Trans retinoic acid can inhibit the proliferation of HSC-T6. HSC-T6 was stimulated by TGF- 尾 1 to down-regulate the expression of COL1 伪 2, MMP-2, MMP-2TIMP-1 mRNA, and it may affect the TGF- 尾 1 / Smad signaling pathway by inhibiting the expression of Smad 2/3, the downstream signal protein of TGF- 尾 1 in HSC-T6, thus exerting its anti-hepatic fibrosis effect.
【作者单位】：西安交通大学第二附属医院医用超声研究室;西安交通大学第一附属医院消化内科;西安交通大学第二附属医院内分泌科;
【分类号】：R575.2

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