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肿瘤坏死因子样弱凋亡诱导因子及其受体对肝星状细胞迁徙的影响
Effect of TNF-like weak inducer of apoptosis and its receptor on migration of hepatic stellate cells
文章发布日期:2017年12月09日  来源:  作者:苏敏,张玮,朱成凯,等  点击次数:418次  下载次数:72次

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【摘要】:目的 探讨肿瘤坏死因子样弱凋亡诱导因子(TWEAK)及其受体成纤维细胞生长因子诱导早期反应蛋白14(Fn14)对肝星状细胞迁徙的影响及其机制。方法 人源性肝星状细胞株LX-2分别予细胞因子TWEAK处理、特异性下调Fn14(Fn14 siRNA)后加入TWEAK处理,Transwell小室检测肝星状细胞迁徙;real-time PCR及Western Blot检测基质金属蛋白酶(MMP)9的表达量。计量资料两组间比较采用独立样本t检验,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果 TWEAK处理组较正常LX-2细胞迁徙能力增强[(105±8)个vs(164±17)个,t=5.287,P<0.01];下调Fn14后加入TWEAK处理的LX-2细胞迁徙数目较阴性对照组减少[(122±9)个vs(58±7)个,t=9.836,P<0.01];TWEAK处理LX-2细胞后,MMP9的mRNA及蛋白水平增加(P值均<0.05),且存在时间依赖性;下调Fn14并加入TWEAK后LX-2细胞MMP9的mRNA及蛋白表达量减少,与单纯TWEAK处理的LX-2细胞组比较,差异有统计学意义(t=5.358,P<0.01)。结论 TWEAK可通过其受体Fn14上调MMP9促进肝星状细胞迁徙,阻断该通路可能成为治疗肝纤维化的一个潜在的新靶点。
【Abstract】:Objective To investigate the effect of TNF-like weak inducer of apoptosis (TWAEK) and its receptor fibroblast growth factor-inducible 14 (Fn14) on the migration of hepatic stellate cells and the possible mechanism. Methods The human hepatic stellate cell line LX-2 cells were treated with TWEAK or Fn14 specific small interfering RNA (Fn14 siRNA)+TWEAK. Transwell chamber was used to observe the migration of hepatic stellate cells, and real-time PCR and Western blot were used to measure the expression of matrix metalloproteinase-9 (MMP9). The independent samples t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with normal LX-2 cells, the TWEAK group had a significant increase in the migration of LX-2 cells (105±8 vs 164±17, t=5.287,P<0.01), and compared with the negative control group, the Fn14 siRNA+TWEAK group had a significant reduction in the number of migrated cells (122±9 vs 58±7, t=9.836, P<0.01). When LX-2 cells were treated with TWEAK, the mRNA and protein expression of MMP9 increased in a time-dependent manner (both P<0.05), while the Fn14 siRNA+TWEAK group had significant reductions in the mRNA and protein expression of MMP9 compared with the TWEAK group (t=5.358, P<0.01). Conclusion TWEAK and its receptor Fn14 can promote the migration of hepatic stellate cells by upregulating MMP9, and blockade of this pathway may become a potential target for the treatment of liver fibrosis.
【关键字】:肝硬化; 肿瘤坏死因子样弱凋亡诱导因子; 成纤维细胞生长因子诱导早期反应蛋白14; 基质金属蛋白酶9
【Key words】:liver cirrhosis; TNF-like weak inducer of apoptosis; fibroblast growth factor-inducible 14; matrix metalloproteinase 9
【引证本文】:SU M, ZHANG W, ZHU CK, et al. Effect of TNF-like weak inducer of apoptosis and its receptor on migration of hepatic stellate cells[J]. J Clin Hepatol, 2018, 34(1): 118-121. (in Chinese)
苏敏, 张玮, 朱成凯, 等. 肿瘤坏死因子样弱凋亡诱导因子及其受体对肝星状细胞迁徙的影响[J]. 临床肝胆病杂志, 2018, 34(1): 118-121.

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