Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress
| Autor: | Mostafa M. Abbas, Latha Ramalingam, Kalhara R. Menikdiwela, Nishan S. Kalupahana, Asha Palat, Naima Moustaid-Moussa, Shane Scoggin, Preethi H. Gunaratne, Halima Bensmail |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine obesity MAP Kinase Signaling System Adipose Tissue White adipocytes Adipose tissue endoplasmic reticulum (ER) stress Inflammation White adipose tissue Article Renin-Angiotensin System Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine miR-690 3T3-L1 Cells Adipocyte medicine Animals Protein kinase A lcsh:QH301-705.5 renin–angiotensin system (RAS) Base Sequence Angiotensin II Endoplasmic reticulum Reproducibility of Results General Medicine Endoplasmic Reticulum Stress Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology Gene Expression Regulation chemistry lcsh:Biology (General) inflammation Unfolded protein response medicine.symptom Biomarkers 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cells, Vol 9, Iss 1327, p 1327 (2020) Cells Volume 9 Issue 6 |
| ISSN: | 2073-4409 |
| Popis: | Overactivation of the renin&ndash 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-&kappa B, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|