title: Hyperoside ameliorates glomerulosclerosis in diabetic nephropathy by downregulating miR-21.
abstract: The purpose of this study was to investigate the therapeutic effects of hyperoside (Hyp) on glomerulosclerosis in diabetic nephropathy and its underlying mechanisms. Blood glucose, kidney mass, and renal function of mice were measured. Renal morphology was observed using hematoxylin and eosin, periodic acid - Schiff's, and Masson's trichrome stain. Fibronectin (FN) and collagen IV (COL IV) in kidney were determined by Western blot and immunohistochemical studies. Matrix metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinase (TIMP)-1 in renal tissues were detected on both the mRNA and protein levels. miRNA expression and artificial alterations by miRNA agomir transfection were evaluated to investigate the protective mechanism of Hyp in mesangial cells. Hyp effectively improved renal function and physiologic features of db/db mice. Hyp also ameliorated glomerulosclerosis by suppressing FN, COL IV, and TIMP-1 expressions and promoting MMP-9 and MMP-2 expressions. The change in MMP-9 mRNA expression was inconsistent with that in protein levels in kidney, indicating that there was a post-transcriptional regulation. Further exploration in vitro showed that miR-21 was downregulated by Hyp, increasing expression of its target, MMP-9. These results suggest that Hyp can ameliorate glomerulosclerosis in diabetic nephropathy by downregulating miR-21 to increase expression of its target, MMP-9.
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: b Department of Cardiovascular Surgery, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Siyi
authors.initials: S
authors.lastname: He
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dai
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: c Department of Applied Chemistry, Chongqing Chemical Industry Vocational College, Chongqing 400020, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: d National Drug Clinical Trial Institution, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Zhou
authors.affiliation: a Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Kebin
authors.initials: K
authors.lastname: Zhang
mesh_terms: D028483:Abelmoschus; D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D010936:Plant Extracts; C021304:hyperoside; D011794:Quercetin
keywords: MMP-9; diabetic nephropathy; glomerulosclerosis; glomérulosclérose; hyperoside; hypéroside; miR-21; néphropathie diabétique