title: MiR-196a Regulates High Glucose-Induced Mesangial Cell Hypertrophy by Targeting p27kip1.
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).
authors: Department of Nephrology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors: Xiaoxia
authors: X
authors: Wang
authors: Department of Ultrasound in Medicine, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors: E
authors: E
authors: Shen
authors: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
authors: Yanzhe
authors: Y
authors: Wang
authors: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
authors: Zhenzhen
authors: Z
authors: Jiang
authors: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
authors: Dingkun
authors: D
authors: Gui
authors: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
authors: Dongsheng
authors: D
authors: Cheng
authors: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
authors: Tingfang
authors: T
authors: Chen
authors: Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China wangniansong2014@163.com.
authors: Niansong
authors: N
authors: Wang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D048429:Cell Size; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C000602251:MIRN196 microRNA, mouse; D035683:MicroRNAs; D005947:Glucose
keywords: diabetic nephropathy; hypertrophy; mesangial cells; miR-196a; p27kip1