title: Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions.
abstract: Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis. This study aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). Microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of α-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, we identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, α-SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice. In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN.
authors.affiliation: Department of Nephrology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.|Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ultrasound in Medicine, Tong Ren Hospital, Shanghai 200336, P. R. China.
authors.forename: E
authors.initials: E
authors.lastname: Shen
authors.affiliation: Department of Nephrology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
authors.forename: Yanzhe
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Dingkun
authors.initials: D
authors.lastname: Gui
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D006984:Hypertrophy; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse