Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress
ORCID
Latha Ramalingam: 0000-0002-4856-7327
Document Type
Article
Date
5-2020
Keywords
adipocytes, endoplasmic reticulum (ER) stress, inflammation, miR-690, obesity, renin–angiotensin system (RAS)
Disciplines
Molecular, Genetic, and Biochemical Nutrition | Other Nutrition
Description/Abstract
Overactivation of the renin-angiotensin system (RAS) during obesity disrupts adipocyte metabolic homeostasis and induces endoplasmic reticulum (ER) stress and inflammation; however, underlying mechanisms are not well known. We propose that overexpression of angiotensinogen (Agt), the precursor protein of RAS in adipose tissue or treatment of adipocytes with Angiotensin II (Ang II), RAS bioactive hormone, alters specific microRNAs (miRNA), that target ER stress and inflammation leading to adipocyte dysfunction. Epididymal white adipose tissue (WAT) from B6 wild type (Wt) and transgenic male mice overexpressing Agt (Agt-Tg) in adipose tissue and adipocytes treated with Ang II were used. Small RNA sequencing and microarray in WAT identified differentially expressed miRNAs and genes, out of which miR-690 and mitogen-activated protein kinase kinase 3 (MAP2K3) were validated as significantly up- and down-regulated, respectively, in Agt-Tg, and in Ang II-treated adipocytes compared to respective controls. Additionally, the direct regulatory role of miR-690 on MAP2K3 was confirmed using mimic, inhibitors and dual-luciferase reporter assay. Downstream protein targets of MAP2K3 which include p38, NF-κB, IL-6 and CHOP were all reduced. These results indicate a critical post-transcriptional role for miR-690 in inflammation and ER stress. In conclusion, miR-690 plays a protective function and could be a useful target to reduce obesity.
Recommended Citation
Menikdiwela KR, Ramalingam L, Abbas MM, Bensmail H, Scoggin S, Kalupahana NS, Palat A, Gunaratne P, Moustaid-Moussa N. Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress. Cells. 2020 May 26;9(6):1327. doi: 10.3390/cells9061327. PMID: 32466437; PMCID: PMC7348980.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
