miR-206 Inhibits Cell Proliferation and Extracellular Matrix Accumulation by Targeting Hypoxia-Inducible Factor 1-alpha (HIF-1α) in Mesangial Cells Treated with High Glucose
Yanchao Cao, Xufen Cao, Lina Sun, Yuanjie Li
Nursing Department, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland)
Med Sci Monit 2019; 25:10036-10044
The goal of this study was to investigate the expression of miR-206 in human glomerular mesangial cells (hMCs) treated by exposure to high glucose (HG) levels, to assess the influence of miR-206 on the proliferation and extracellular matrix (ECM) deposition of hMCs, and to investigate the potential mechanisms of action.
MATERIAL AND METHODS: The level of miR-206 was detected by RT-qPCR. MTT assay and colony formation assay were used to assess hMCs cell proliferation ability. Western blotting was carried out to measure the expression of related proteins. Bioinformatics software (http://www.targetscan.org) was used to predict the potential target genes of miR-206, and dual-luciferase reporter assay was used to confirm this prediction.
RESULTS: Our results suggest that the level of miR-206 was downregulated in HG-treated hMCs. Cell proliferation was promoted in HG-induced hMCs, while this phenomenon was significantly reversed with miR-206 mimics. miR-206 mimics significantly enhanced p21 expression and decreased cyclin D1 and CDK2 expressions, but the opposite was found in HG-induced hMCs. Moreover, the level of ECM proteins was notably increased in hMCs treated with HG, which was also significantly reversed by miR-206 mimics. miR-206 inhibitor had the opposite effects. Furthermore, HIF-1alpha was found to be a direct target of miR-206, and was negatively regulated by miR-206 in hMCs. miR-206 can target HIF-1alpha to modulate cell proliferation and ECM accumulation.
CONCLUSIONS: Collectively, our results suggest that miR-206 plays a vital role in HG-treated hMCs through inhibiting cell proliferation and ECM accumulation, partly via targeting HIF-1alpha.
Keywords: Diabetic Nephropathies, Extracellular Matrix, mesangial cells, MicroRNAs