MicroRNA-122 aggravates angiotensin II-mediated apoptosis and autophagy imbalance in rat aortic adventitial fibroblasts via the modulation of SIRT6-elabela-ACE2 signaling.

European Journal of Pharmacology
Juan-Juan SongJiu-Chang Zhong

Abstract

Abnormal aortic adventitial fibroblasts (AFs) play essential roles in the development of vascular remodeling and disorders. Previous studies revealed that microRNA-122 (miR-122) levels were elevated in the aortic adventitia of hypertensive rats with vascular injury. Here, we aim to evaluate the biological effects and underlying mechanisms of miR-122 in rat AFs. Exposure to angiotensin II (ATII) in rat AFs resulted in decreased levels of sirtuin 6 (SIRT6), elabela (ELA), and angiotensin-converting enzyme 2 (ACE2). Additionally, stimulation with ATII contributed to a decline in autophagic flux and obvious increases in cellular migration, oxidative stress, and apoptosis, which were exacerbated by the transfection of miR-122-5p mimic but were rescued by miR-122-5p inhibitor, exogenous replenishment of ELA, and recombinant adeno-associated virus expressing SIRT6 (rAAV-SIRT6), respectively. Moreover, stimulation with miR-122-5p mimic led to a marked reduction in the levels of SIRT6 and ELA in rat AFs, which were elevated by stimulation with rAAV-SIRT6. Furthermore, miR-122-5p inhibitor-mediated pro-autophagic, anti-oxidant and anti-apoptotic effects in rat AFs were partially suppressed by 3-methyladenine, SIRT6 small interfering RNA ...Continue Reading

Citations

Aug 29, 2020·Cardiovascular Toxicology·Ying LiuJiu-Chang Zhong
Mar 4, 2021·Journal of Cellular and Molecular Medicine·Xuejun GeJie Du
Mar 31, 2021·Molecular and Cellular Endocrinology·Nihal KaplanRobert M Lavker
Apr 23, 2021·International Journal of Biological Macromolecules·Zelalai SimayiNigary Yadikar

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Methods Mentioned

BETA
transfection
flow cytometry

Software Mentioned

FlowJo
Image J
TargetScanHuman
SPSS Statistics

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