title: Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats.
abstract: This study was designed to assess whether the glomerular expression of mRNA for extracellular matrix (ECM) components including alpha 1 (I), alpha 1 (III), and alpha 1 (IV) collagen chains, laminin B1 and B2 chains, metalloproteinases (MMP), and tissue inhibitor of metalloproteinases (TIMP) is affected by enalapril in 12- and 24-wk-old rat after streptozotocin injection. Animals were divided into three groups; untreated diabetic rats, enalapril-treated diabetic rats, and control rats. Enalapril treatment was continued for 24 wk. Enalapril reduced both creatinine clearance (P < 0.01) and urinary protein excretion (P < 0.01) in diabetic rats. In diabetic rats, mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly at 24 wk compared with those in controls [alpha 1(IV): 3.8-fold (P < 0.01); laminin B1: 6.2-fold (P < 0.01); laminin B2:5.4-fold (P < 0.01), alpha 1(i): 4.8-fold (P < 0.01) and alpha 1(III): 3.8-fold (P < 0.01)]. At 24 wk, mRNA levels for MMP-1 and MMP-3 fell to 40% (P < 0.01) and 20% (P < 0.01), respectively, in the glomeruli of diabetic rats compared with levels in controls. In contrast, mRNA levels for TIMP-1 and TIMP-2 increased significantly at 24 wk after streptozotocin injection (TIMP-1: 8.0-fold (P < 0.01) and TIMP-2: 6.4-fold (P < 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Fukui
authors.forename: I
authors.initials: I
authors.lastname: Ebihara
authors.forename: S
authors.initials: S
authors.lastname: Osada
authors.forename: Y
authors.initials: Y
authors.lastname: Tomino
authors.forename: H
authors.initials: H
authors.lastname: Koide
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology; D004656:Enalapril / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D004656:Enalapril; D008666:Metalloendopeptidases