Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress

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dc.creatorMenikdiwela, Kalhara R. (TTU)
dc.creatorRamalingam, Latha (TTU)
dc.creatorAbbas, Mostafa M.
dc.creatorBensmail, Halima
dc.creatorScoggin, Shane (TTU)
dc.creatorKalupahana, Nishan S. (TTU)
dc.creatorPalat, Asha
dc.creatorGunaratne, Preethi
dc.creatorMoustaid-Moussa, Naima (TTU)
dc.date.accessioned2023-03-30T17:20:49Z
dc.date.available2023-03-30T17:20:49Z
dc.date.issued2020
dc.descriptioncc-by
dc.description.abstractOveractivation 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.
dc.identifier.citationMenikdiwela, K.R., Ramalingam, L., Abbas, M.M., Bensmail, H., Scoggin, S., Kalupahana, N.S., Palat, A., Gunaratne, P., & Moustaid-Moussa, N.. 2020. Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress. Cells, 9(6). https://doi.org/10.3390/cells9061327
dc.identifier.urihttps://doi.org/10.3390/cells9061327
dc.identifier.urihttps://hdl.handle.net/2346/92123
dc.language.isoeng
dc.subjectadipocytes
dc.subjectendoplasmic reticulum (ER) stress
dc.subjectinflammation
dc.subjectmiR-690
dc.subjectobesity
dc.subjectrenin–angiotensin system (RAS)
dc.titleRole of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress
dc.typeArticle

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