Lamin A/C negatively regulated by miR-124-3p modulates apoptosis of vascular smooth muscle cells during cyclic stretch application in rats.
Acta Physiol (Oxf)
; 228(3): e13374, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31495066
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Miócitos de Músculo Liso
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Lamina Tipo A
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MicroRNAs
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Hipertensão
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article