title: MicroRNA-27a Induces Mesangial Cell Injury by Targeting of PPARγ, and its In Vivo Knockdown Prevents Progression of Diabetic Nephropathy.
abstract: MicroRNAs play important roles in the pathogenesis of diabetic nephropathy (DN). In this study, we found that high glucose upregulated miR-27a expression in cultured glomerular mesangial cells and in the kidney glomeruli of streptozotocin (STZ)-induced diabetic rats. miR-27a knockdown prevented high glucose-induced mesangial cell proliferation and also blocked the upregulation of extracellular matrix (ECM)-associated profibrotic genes. Reduction of cell proliferation and profibrotic gene expression by a miR-27a inhibitor depended upon the expression of peroxisome proliferator-activated receptor γ (PPARγ). Further studies showed that miR-27a negatively regulated PPARγ expression by binding to the 3'-untranslated region of rat PPARγ. An antisense oligonucleotide specific to miR-27a (antagomir-27a) significantly reduced renal miR-27a expression in STZ-induced diabetic rats and significantly increased PPARγ levels. Antagomir-27a also reduced kidney ECM accumulation and proteinuria in STZ-induced diabetic rats. These findings suggest that specific reduction of renal miR-27a decreases renal fibrosis, which may be explained in part by its regulation of PPARγ, and that targeting miR-27a may represent a novel therapeutic approach for DN.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wu
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Ji
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Guijun
authors.initials: G
authors.lastname: Qin
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism; D050527:Mesangial Cells / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats
chemical_list: D035683:MicroRNAs; D047495:PPAR gamma; D005947:Glucose