Basic & Clinical Medicine ›› 2021, Vol. 41 ›› Issue (3): 364-369.

• Original Articles • Previous Articles     Next Articles

Over-expression of c-SKI inhibits isoprenaline-induced myocardial fibrosis in mice

ZHANG Ying, XIANG Yan, ZHANG Yue, WANG Juan*   

  1. Department of Cardiology, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China
  • Received:2020-04-06 Revised:2020-06-30 Online:2021-03-05 Published:2021-03-01
  • Contact: *15160991696@163.com

Abstract: Objective To investigate the effect of c-SKI on isoprenaline(ISO)-induced cardiac fibrosis in mice. Methods Mice were divided into 4 groups: the control group,the model group,the c-SKI gene infection group (LV-SKI group) and the normal control virus infection group (LV-NC group), with 10 in each. After two weeks, in the model group, isoprenaline(ISO) was injected subcutaneously for 30 d, with the first dose of 5 mg/kg followed by 2.5 mg/kg. In the LV-SKI group and the LV-NC group, c-SKI lentivirus and control virus were injected into the tail vein on days 18, 21, 24, 27 and 30 at a dose of 100 μL, titer was 1×108 TU.HE staining and Masson staining was used to observe the pathological changes of myocardial tissue. ELISA was used to detect type Ⅰ and type Ⅲ collagen in myocardial tissue. Western blot was used to detect the expression of c-SKI, interstitial cell marker vimentin, α SMA,endothelial cell marker CD31 and the expression levels of transcription factors Snail, Twist and Slug. Results Compared with the control group, the expression of c-ski in the model group was time-dependent (P<0.01). In the model group, the myocardial cells were disordered, the interstitium was significantly increased, and the contents of type Ⅰ and type Ⅲ collagen were increased (P<0.01). Expressions of vimentin, α-SMA, Snail, Twist and Slug were all up regulated, while CD31 protein expression was down-regulated(P<0.05). After over-expressing c-SKI, compared with the LV-NC group, the myocardial structure of the mice tended to be neat, the interstitial collagen fibers decreased, and the type Ⅰ and Ⅲ collagen in the myocardial tissue decreased (P<0.01). The expression of vimentin and belt-sma was down-regulated (P<0.05), and the expression of CD31 was up-regulated (P<0.05). Meanwhile, the expression of transcription factors Snail, Twist and Slug was also down-regulated (P<0.01). Conclusions c-SKI expression is down-regulated during myocardial fibrosis in mice, and over-expression of c-SKI can improve ISO-induced myocardial fibrosis by inhibiting End-MT.

Key words: c-SKI, cardiac fibrosis, endothelial-mesenchymal transition (End-MT), transcription factor

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