title: FK506 ameliorates renal injury in early experimental diabetic rats induced by streptozotocin.
abstract: Calcineurin (CaN) plays an important role in glomerular hypertrophy and extracellular matrix accumulation in early diabetic nephropathy. Cyclosporine (CSA), a CaN inhibitor, has been shown to reduce renal injury in streptozotocin-induced diabetic rats. We examined whether FK506, which immunosuppressive action was 10-100 times of CSA, inhibits progression of diabetic nephropathy in experimental diabetic rats. Diabetes was induced with streptozotocin in rats, and FK506 (0.5 or 1.0mg/kg) was orally administered once a day for 4 weeks. Increased relative kidney weight was significantly reduced by FK506 treatment with 1.0mg/kg (p<0.05), and elevated 24 hour urinary albumin excretion rate was markedly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05, 0.01). Elevated glomerular volume was significantly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05), and increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0mg/kg (p<0.01). Western blot analysis noted that the expression of CaN protein was increased 2.4 fold in the kidney from diabetic rats, and FK506 treatment with 0.5 and 1.0mg/kg could reduce increased expression of CaN protein by 38.0% and 73.2%. The expression of 1α (IV) collagen, p65, p-p65, OPN, α-SMA and TGF-β1 protein in kidney was significantly increased in diabetic rats and reduced by FK506 treatment (p<0.05, 0.01). Our results show that FK506 could ameliorate renal injury in early experimental diabetic rats, which mechanism may be at least partly correlated with suppression on increased CaN in renal tissue in diabetic rats.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Qi
authors.forename: Yong-Gui
authors.initials: YG
authors.lastname: Wu
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Ji-Jia
authors.initials: JJ
authors.lastname: Shen
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000517:prevention & control; D018450:Disease Progression; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016559:Tacrolimus / Q000008:administration & dosage*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D019703:Calcineurin; D024141:Collagen Type IV; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D007166:Immunosuppressive Agents; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016559:Tacrolimus; D053773:Transforming Growth Factor beta1; C529605:OPHN1 protein, rat; C063447:p65 oncofetal mRNA transport protein, rat; C498862:Acta2 protein, rat