Smooth muscle-specific HuR knockout induces defective autophagy and atherosclerosis
| Autor: | Jianmin Yang, Cheng Zhang, Shanshan Liu, Wencheng Zhang, Hongxuan Li, Jingjing Wang, Xiuxin Jiang, Xiuru Cui, Shangming Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Immunology Pathogenesis Article Muscle Smooth Vascular ELAV-Like Protein 1 Gene Knockout Techniques Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Smooth muscle Antigen Autophagy Animals Medicine lcsh:QH573-671 Protein kinase A Mice Knockout business.industry lcsh:Cytology AMPK Translation (biology) Cell Biology Atherosclerosis Adenosine Cardiovascular diseases 030104 developmental biology 030220 oncology & carcinogenesis Cancer research business Homeostasis medicine.drug |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 4, Pp 1-14 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Human antigen R (HuR) is a widespread RNA-binding protein involved in homeostatic regulation and pathological processes in many diseases. Atherosclerosis is the leading cause of cardiovascular disease and acute cardiovascular events. However, the role of HuR in atherosclerosis remains unknown. In this study, mice with smooth muscle-specific HuR knockout (HuRSMKO) were generated to investigate the role of HuR in atherosclerosis. HuR expression was reduced in atherosclerotic plaques. As compared with controls, HuRSMKO mice showed increased plaque burden in the atherosclerotic model. Mechanically, HuR could bind to the mRNAs of adenosine 5′-monophosphate-activated protein kinase (AMPK) α1 and AMPKα2, thus increasing their stability and translation. HuR deficiency reduced p-AMPK and LC3II levels and increased p62 level, thereby resulting in defective autophagy. Finally, pharmacological AMPK activation induced autophagy and suppressed atherosclerosis in HuRSMKO mice. Our findings suggest that smooth muscle HuR has a protective effect against atherosclerosis by increasing AMPK-mediated autophagy. |
| Databáze: | OpenAIRE |
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