title: Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice.
abstract: OBJECTIVE
  Obesity is recognized increasingly as a major risk factor for kidney disease. We reported previously that plasma adiponectin levels were decreased in obesity, and that adiponectin had defensive properties against type 2 diabetes and hypertension. In this study, we investigated the role of adiponectin for kidney disease in a subtotal nephrectomized mouse model.
  
  
  RESULTS
  Subtotal (5/6) nephrectomy was performed in adiponectin-knockout (APN-KO) and wild-type (WT) mice. The procedure resulted in significant accumulation of adiponectin in glomeruli and interstitium in the remnant kidney. Urinary albumin excretion, glomerular hypertrophy, and tubulointerstitial fibrosis were significantly worse in APN-KO mice compared with WT mice. Intraglomerular macrophage infiltration and mRNA levels of vascular cell adhesion molecule (VCAM)-1, MCP-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, collagen type I/III, and NADPH oxidase components were significantly increased in KO mice compared with WT mice. Treatment of APN-KO mice with adenovirus-mediated adiponectin resulted in amelioration of albuminuria, glomerular hypertrophy, and tubulointerstitial fibrosis and reduced the elevated levels of VCAM-1, MCP-1, TNF-alpha, TGF-beta1, collagen type I/III, and NADPH oxidase components mRNAs to the same levels as those in WT mice.
  
  
  CONCLUSIONS
  Adiponectin accumulates to the injured kidney, and prevents glomerular and tubulointerstitial injury through modulating inflammation and oxidative stress.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Iwatani
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Komura
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.forename: Fumie
authors.initials: F
authors.lastname: Katsube
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Takahito
authors.initials: T
authors.lastname: Ito
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000419:Albuminuria / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009392:Nephrectomy; D018384:Oxidative Stress
chemical_list: D052242:Adiponectin