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

苏敏; 张玮; 朱成凯; 张峰; 诸葛宇征

doi:10.3969/j.issn.1001-5256.2018.01.024

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

DOI: 10.3969/j.issn.1001-5256.2018.01.024

南京大学医学院附属鼓楼医院消化科

基金项目:

国家自然科学基金资助项目(8157040652)；

详细信息

中图分类号: R575.2
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出版历程
- 出版日期: 2018-01-20

Effect of TNF-like weak inducer of apoptosis and its receptor on migration of hepatic stellate cells

Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210000, China

Research funding:

摘要

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...
- 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
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.
- liver cirrhosis /
- TNF-like weak inducer of apoptosis /
- fibroblast growth factor-inducible 14 /
- matrix metalloproteinase 9

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