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MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism.

ABSTRACT: Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs). Overactivation of IGF signaling has been implicated in promoting the aging process. Lectin?like oxidized low?density lipoprotein (oxLDL) receptor?1 (LOX?1) is a scavenger receptor that mediates the internalization of oxLDL into cells. Previous studies by our group have indicated that microRNA let?7g exerts an anti?aging effect on ECs and also suppresses LOX-1 expression. Since LOX?1 also induces the aging process, the present study we explored whether let?7g still exerts an anti?aging effect on ECs when LOX?1 is suppressed. Angiotensin II (Ang II) was used to induce senescence in ECs. It was revealed that Ang II significantly increased the expression of aging markers, including ??galactosidase, LOX?1, IGF1 and its receptor IGF1R. On the contrary, Ang II decreased the expression of the anti?aging gene sirtuin 1 (SIRT1). When LOX?1 was knocked down by small interfering RNA, let?7g still dose?dependently decreased the expression of ??galactosidase (??gal), LOX?1, IGF1 and IGF1R, and SIRT1 was still upregulated. Using senescence?associated ??gal staining, it was confirmed that let?7g exerts a LOX?1?independent anti?aging effect on ECs. In conclusion, the present study demonstrated that let?7g has an anti?aging effect regardless of the presence or absence of LOX-1.

SUBMITTER: Hsu PY

PROVIDER: S-EPMC5810198 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism.

Hsu Po-Yuan PY Lin Wen-Yi WY Lin Ruey-Tay RT Juo Suh-Hang H SH

International journal of molecular medicine 20180123 4

Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs). Overactivation of IGF signaling has been implicated in promoting the aging process. Lectin‑like oxidized low‑density lipoprotein (oxLDL) receptor‑1 (LOX‑1) is a scavenge ...[more]

PMID: 29393358

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Project description:Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation and oxidative stress, all of which may contribute to renal damage. MicroRNAs (miRs/miRNAs) play a crucial regulatory role in the pathogenesis of hypertensive nephropathy (HN). The present study aimed to assess the differential expression profiles of potential candidate genes involved in Ang II-induced rat renal artery endothelial cell (RRAEC) dysfunction and explore their possible functions. In the present study, the changes in energy metabolism and autophagy function in RRAECs were evaluated using the Seahorse XF Glycolysis Stress Test and dansylcadaverine/transmission electron microscopy following exposure to Ang II. Subsequently, mRNA-miRNA sequencing experiments were performed to determine the differential expression profiles of mRNAs and miRNAs. Integrated bioinformatics analysis was applied to further explore the molecular mechanisms of Ang II on endothelial injury induced by Ang II. The present data supported the notion that Ang II upregulated glycolysis levels and promoted autophagy activation in RRAECs. The sequencing data demonstrated that 443 mRNAs and 58 miRNAs were differentially expressed (DE) in response to Ang II exposure, where 66 mRNAs and 55 miRNAs were upregulated, while 377 mRNAs and 3 miRNAs were downregulated (fold change >1.5 or <0.67; P<0.05). Functional analysis indicated that DE mRNA and DE miRNA target genes were mainly associated with cell metabolism (metabolic pathways), differentiation (Th1 and Th2 cell differentiation), autophagy (autophagy-animal and autophagy-other) and repair (RNA-repair). To the best of the authors' knowledge, this is the first report on mRNA-miRNA integrated profiles of Ang II-induced RRAECs. The present results provided evidence suggesting that the miRNA-mediated effect on the 'mTOR signaling pathway' might play a role in Ang II-induced RRAEC injury by driving glycolysis and autophagy activation. Targeting miRNAs and their associated pathways may provide valuable insight into the clinical management of HN and may improve patient outcome.

Dataset Information

MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism.

Publications

MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism.

Similar Datasets

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