MiR-196a Regulates High Glucose-Induced Mesangial Cell Hypertrophy by Targeting p27kip1. (August 2015)

• Record Type: Journal Article
• Authors: Wang, Xiaoxia; Shen, E.; Wang, Yanzhe; Jiang, Zhenzhen; Gui, Dingkun; Cheng, Dongsheng; Chen, Tingfang; Wang, Niansong
• Other Names: Ding Xianting guest-editor.
• Is Part Of: Journal of laboratory automation. Volume 20:Number 4(2015:Aug.)
• Page Start: 491
• Page End: 499
• Publication Date: 2015-08
• Subjects: miR-196a -- diabetic nephropathy -- mesangial cells -- hypertrophy -- p27kip1; Medical laboratory technology -- Periodicals; Laboratories -- Equipment and supplies -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.075
• DOI: 10.1177/2211068215569055
• Languages: English
• ISSNs: 2211-0682

Abstract

Glomerular mesangial cell (MC) hypertrophy is regarded as one of the earliest pathological characteristics of diabetic nephropathy (DN), which plays a critical role in the pathogenesis of glomerulosclerosis. This study investigated the role of microRNAs (miRNAs) in MC hypertrophy due to exposure to high glucose. With a microarray, we screened the differential profiles of miRNAs in the renal cortex of DN mice, as verified by reverse transcription PCR with subsequent analysis of bioinformatics. We found miR-196a was downregulated remarkably in DN mice and increased the hypertrophy-related gene of p27 kip1 in high-enrichment gene ontologies. Furthermore, transfection of the miR-196a mimic greatly inhibited the expression of p27 kip1 with recovery of MC hypertrophic morphology. With flow cytometry, we also found that overexpression of miR-196a significantly reduced the percentage of G1 phase arrest in the cell cycle. Cotransfection of the miR-196a mimic with a wild type of 3′ UTR of the p27 kip1 vector reduced the activity of the luciferase reporter significantly in contrast to the miR-196a mimic with a mutant of the counterpart in HEK293 cell lines, suggesting that miR-196a directly targets p27 kip1 . Finally, knockdown of p27 kip1 with specific small interfering RNA in MCs substantially reversed MC hypertrophy induced by transfection of the miR-196a inhibitor. This study revealed that miR-196a acts as an important molecular regulator in high glucose-induced MC hypertrophy by targeting p27 kip1 .