MicroRNA-22 Inhibits the Apoptosis of Vascular Smooth Muscle Cell by Targeting p38MAPKα in Vascular Remodeling of Aortic Dissection
| Autor: | Zaiping Jing, Xiang Ma, Qing Jing, Jian Zhou, Lei Zhang, Chen Wang, Wen Tian, Wang Jiannan, Yudong Sun, Zhiqing Zhao, Li Zhenjiang, Yu Xiao, Guokun Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Small interfering RNA Vascular smooth muscle p38 mitogen-activated protein kinases miR-22 vascular remodeling microRNA 22 Biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Drug Discovery microRNA aortic dissection Protein kinase A Gene knockdown lcsh:RM1-950 apoptosis Cell biology 030104 developmental biology lcsh:Therapeutics. Pharmacology Apoptosis 030220 oncology & carcinogenesis cardiovascular system Molecular Medicine Original Article vascular smooth muscle cell |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 22, Iss, Pp 1051-1062 (2020) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | MicroRNA 22 (miR-22) was found in diverse cardiovascular diseases to have a role in regulating multiple cellular processes. However, the regulatory role of miR-22 in aortic dissection (AD) was still unclear. The miR-22 expression in human aorta was explored. A series of mimic, inhibitor, or small interfering RNA (siRNA) plasmids were delivered into vascular smooth muscle cells (VSMCs) to explore the effects of miR-22 and p38 mitogen-activated protein kinase α (p38MAPKα) in controlling VSMC apoptosis in vitro. In addition, a mouse AD model was established, and histopathologic analyses were performed to evaluate the regulatory effects of miR-22. Reduced miR-22 and increased apoptosis of VSMCs was seen in human AD aorta. Downregulation of miR-22 increased the apoptosis of VSMCs in vitro. Bioinformatics analyses revealed that p38MAPKα was a target of miR-22. Inhibiting p38MAPKα expression could reverse the apoptosis of VSMCs induced by miR-22 downregulation. Knockdown of miR-22 in the AD mouse model significantly promoted the development of AD. Our data underscore the importance of vascular remodeling and VSMC function in AD. miR-22 may represent a new therapeutic approach for AD by regulating the apoptosis of VSMCs through the MAPK signaling pathway. Graphical Abstract This study indicates miR-22 may represent a new therapeutic approach for aortic dissection by regulating the apoptosis of VSMCs through the MAPK signaling pathway. The study provided a novel insight into the mechanism of AD and the innovative therapeutic strategies in the form of new targets for small molecule therapies. |
| Databáze: | OpenAIRE |
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