title: 3,5-Diiodo-l-thyronine ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats.
abstract: 3, 5-Diiodothyronine (T2), a natural metabolite of triiodothyronine (T3) from deiodination pathway, can mimic biologic effects of T3 without inducing thyrotoxic effects. Recent studies revealed T3 acted as a protective factor against diabetic nephropathy (DN). Nevertheless, little is known about the effect of T2 on DN. This study was designed to investigate whether and how T2 affects experimental models of DN in vivo and in vitro. Administration of T2 was found to prevent significant decrease in SIRT1 protein expression and activity as well as increases in blood glucose, urine albumin excretion, matrix expansion, transforming growth factor-β1 expression, fibronectin and type IV collagen deposition in the diabetic kidney. Concordantly, similar effects of T2 were exhibited in the cultured rat mesangial cells (RMC) exposed to high glucose and that could be abolished by a known SIRT1 inhibitor, sirtinol. Moreover, enhanced NF-κB acetylation and JNK phosphorylation present in both diabetic rats and high glucose-treated RMC were distinctly dampened by T2. Collectively, these results suggested that T2 was a protective agent against renal damage in diabetic nephropathy, whose action involved regulation of SIRT1.
authors: Department of Pathology, Fudan University, Shanghai, People's Republic of China.
authors: Guoguo
authors: G
authors: Shang
authors: Pan
authors: P
authors: Gao
authors: Zhonghua
authors: Z
authors: Zhao
authors: Qi
authors: Q
authors: Chen
authors: Tao
authors: T
authors: Jiang
authors: Nong
authors: N
authors: Zhang
authors: Hui
authors: H
authors: Li
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004104:Diiodothyronines / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004104:Diiodothyronines; D005353:Fibronectins; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; C030103:3,5-diiodothyronine; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose