中国病理生理杂志2021，Vol.37Issue(5)：798-808,11.DOI:10.3969/j.issn.1000-4718.2021.05.004
TXNIP通过诱导氧化应激促进心肌纤维化的发生
Thioredoxin-interacting protein contributes to cardiac fibrosis by elevating oxidative stress in cardiac fibroblasts
摘要
Abstract
AIM:To explore the role of thioredoxin-interacting protein(TXNIP)in mediating cardiac fibro-sis. METHODS:In vivo,4 weeks of angiotensin(Ang)Ⅱ infusion was used to induced fibrogenesis in the heart of the mice. In vitro,cardiac fibroblasts(CFs)isolated from neonatal rats were treated with Ang Ⅱ at different concentrations for different durations. The protein expression of TXNIP in the hearts of the mice and CFs was detected by Western blot. The CFs were pretreated with losartan(an Ang Ⅱ type 1 receptor blocker)prior to Ang Ⅱ stimulation,and then TXNIP expres-sion was detected by immunofluorescence and Western blot. Subsequently,after knock-down of TXNIP by siRNA,multi-ple methods including wound healing assay,crystal violet staining,Western blot and ROS detection were used to analyze the changes in cell migration,expression of fibrosis-related proteins collagen type Ⅰ(Col Ⅰ),collagen type Ⅲ(Col Ⅲ),vi-mentin and α-smooth muscle actin (α-SMA),oxidative stress and MAPK signaling in CFs exposed to Ang Ⅱ. RE-SULTS:In vivo,TXNIP was up-regulated in the hearts of mice with cardiac fibrosis. In vitro,TXNIP was induced by Ang Ⅱ in a dose-and time-dependent manner,but this increase was reversed by losartan. TXNIP knock-down inhibited Ang Ⅱ-induced cell migration and decreased the protein levels of α-SMA,vimentin,Col Ⅰ and Col Ⅲ in Ang Ⅱ-treated CFs. Nota-bly,TXNIP knock-down alleviated cellular oxidative stress and suppressed the activated MAPK signaling pathway in CFs under Ang Ⅱ stimulation. CONCLUSION:TXNIP may participate in the pathogenesis of cardiac fibrosis through pro-moting oxidative stress via MAPK signaling pathway,suggesting that TXNIP may be a promising therapeutic target for treatment of cardiac fibrosis.关键词
心肌纤维化/硫氧还蛋白相互作用蛋白/氧化应激/血管紧张素Ⅱ/MAPK信号通路Key words
Cardiac fibrosis/Thioredoxin-interacting protein/Oxidative stress/Angiotensin Ⅱ/MAPK sig-naling pathway分类
医药卫生引用本文复制引用
彭琳茜,杨佳丹,王瑞钰,李兴兵,杨茜洋,成哲,吕鼎一,阎江洪,张美霞,尚飞飞..TXNIP通过诱导氧化应激促进心肌纤维化的发生[J].中国病理生理杂志,2021,37(5):798-808,11.基金项目
Supported by the National Natural Science Foundation of China(No.81603330) （No.81603330）
