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- Title
Lamin A/C negatively regulated by miR‐124‐3p modulates apoptosis of vascular smooth muscle cells during cyclic stretch application in rats.
- Authors
Bao, Han; Li, Hai‐Peng; Shi, Qian; Huang, Kai; Chen, Xiao‐Hu; Chen, Yuan‐Xiu; Han, Yue; Xiao, Qian; Yao, Qing‐Ping; Qi, Ying‐Xin
- Abstract
Aim: Apoptosis of vascular smooth muscle cells (VSMCs) influenced by abnormal cyclic stretch is crucial for vascular remodelling during hypertension. Lamin A/C, a nuclear envelope protein, is mechano‐responsive, but the role of lamin A/C in VSMC apoptosis is still unclear. Methods: FX‐5000T Strain Unit provided cyclic stretch (CS) in vitro. AnnexinV/PI and cleaved Caspase 3 ELISA detected apoptosis. qPCR was used to investigate the expression of miR‐124‐3p and a luciferase reporter assay was used to evaluate the ability of miR‐124‐3p binding to the Lmna 3'UTR. Protein changes of lamin A/C and relevant molecules were detected using western blot. Ingenuity Pathway Analysis and Protein/DNA array detected the potential transcription factors. Renal hypertensive rats verified these changes. Results: High cyclic stretch (15%‐CS) induced VSMC apoptosis and repressed lamin A/C expressions compared with normal (5%‐CS) control. Downregulation of lamin A/C enhanced VSMC apoptosis. In addition, 15%‐CS had no significant effect on mRNA expression of Lmna, and lamin A/C degradation was not induced by autophagy. 15%‐CS elevated miR‐124‐3p bound to the 3'UTR of Lmna and negatively regulated protein expression of lamin A/C. Similar changes occurred in renal hypertensive rats compared with sham controls. Lamin A/C repression affected activity of TP53, CREB1, MYC, STAT1/5/6 and JUN, which may in turn affect apoptosis. Conclusion: Our data suggested that the decreased expression of lamin A/C upon abnormal cyclic stretch and hypertension may induce VSMC apoptosis. These mechano‐responsive factors play important roles in VSMC apoptosis and might be novel therapeutic targets for vascular remodelling in hypertension.
- Subjects
VASCULAR smooth muscle; MUSCLE cells; NUCLEAR membranes; HYPERTENSION; NUCLEAR proteins
- Publication
Acta Physiologica, 2020, Vol 228, Issue 3, p1
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/apha.13374