Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice.
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.
Ohashi
Koji
K
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Iwatani
Hirotsugu
H
Kihara
Shinji
S
Nakagawa
Yasuhiko
Y
Komura
Noriyuki
N
Fujita
Koichi
K
Maeda
Norikazu
N
Nishida
Makoto
M
Katsube
Fumie
F
Shimomura
Iichiro
I
Ito
Takahito
T
Funahashi
Tohru
T
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
D052242:Adiponectin