title: Renoprotective effects of fenofibrate in diabetic rats are achieved by suppressing kidney plasminogen activator inhibitor-1.
abstract: To investigate mechanisms of protective effects of fenofibrate on the diabetic kidney, male Wistar rats were divided into control, untreated diabetes, and fenofibrate-treated (32 mg kg(-1) d(-1), 8 weeks) diabetes groups. Diabetes induced by streptozotocin (25 mg/kg) and a high-fat diet was characterized by the disorders of plasma glucose and lipids. In untreated diabetic rats, there were increases in glomerular volume, matrix content, expressions of laminin and urinary albumin excretion. These nephropathies were associated with the upregulations of plasminogen activator inhibitor 1 (PAI-1) mRNA expression and its protein activity in the renal cortex, and a significant increase in transforming growth factor beta1 (TGF-beta1) expression. Treatment with fenofibrate suppressed the expression of PAI-I mRNA and its protein activity, and inhibited TGF-beta1 overexpression. It also partially reversed metabolic disorders and pathophysiologic changes associated with diabetic nephropathy. Our results indicate that fenofibrate delays the progression of diabetic nephropathy in rats to some extent. These renoprotective effects are likely to be achieved through suppression of PAI-1 and TGF-beta1 in the renal cortex, and consequently less extracellular matrix deposition.
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. cheria_chen@sohu.com
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Chen
authors.forename: Jiao-Yue
authors.initials: JY
authors.lastname: Zhang
authors.forename: Bao-Ping
authors.initials: BP
authors.lastname: Wang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007797:Laminin / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D007797:Laminin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D005947:Glucose; D011345:Fenofibrate