title: Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice.
abstract: The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Chen
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Du
authors.affiliation: Department of Gerontology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Peng
authors.affiliation: Department of Emergency, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Zhao-Zhong
authors.initials: ZZ
authors.lastname: Xu
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Niu
authors.affiliation: Department of Nephrology, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Long
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D000077405:Irbesartan; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013777:Tetrazoles; D000077405:Irbesartan