title: Adiponectin reduces proteinuria in streptozotocin-induced diabetic Wistar rats.
abstract: The aim of the paper is to investigate the effects of adiponectin in diabetic nephropathy; we used an adenovirus to over-express adiponectin (Ad-Adipo) in streptozotocin (STZ)-induced diabetic rats. Animals were injected with either Ad-Adipo or control Ad-lacZ at 10 weeks after STZ treatment, and at two weeks postadenovirus injection, renal function was assessed. The degree of proteinuria was significantly reduced in Ad-Adipo rats compared with Ad-lacZ rats. Consistent with this, the mRNA expression levels of nephrin and transforming growth factor β (TGF-β) were significantly increased and decreased in the renal cortex of Ad-Adipo rats, respectively. Moreover, adiponectin over-expression in STZ rats decreased markers of endothelial dysfunction, a feature of diabetic nephropathy disease progression. Endothelin 1 (ET-1), plasminogen activator inhibitor 1 (PAI-1) and inducible nitric oxide synthase (iNOS) mRNA expression levels were significantly reduced in the renal cortex of Ad-Adipo rats, respectively. Concurrently, mRNA expression levels of endothelial nitric oxide synthase (eNOS), a positive regulator of endothelial function, were significantly increased in the renal cortex of Ad-Adipo rats. We have shown that chronic hyperadiponectinemia significantly alleviated the progression of proteinuria in early stage diabetic nephropathy. The mechanism whereby adiponectin decreases proteinuria involves an increase in nephrin expression, and an improvement of the endothelial dysfunction due to decreases in ET-1 and PAI-1, and an increase in eNOS expression in the renal cortex. Thus, over-expression of adiponectin has beneficial effects on early stage diabetic nephropathy.
authors.affiliation: Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima-City, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakamaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Satoh
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kudoh
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011507:Proteinuria / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D019332:Endothelin-1; D008565:Membrane Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C113267:nephrin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III