Enalapril attenuates increased gene expression of extracellular matrix components in diabetic rats

J Am Soc Nephrol. 1995 Jan;5(7):1492-7. doi: 10.1681/ASN.V571492.

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / physiopathology
  • Enalapril / pharmacology*
  • Extracellular Matrix Proteins / genetics*
  • Gene Expression / drug effects*
  • Glycoproteins / genetics
  • Male
  • Metalloendopeptidases / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Inhibitor of Metalloproteinases

Substances

  • Extracellular Matrix Proteins
  • Glycoproteins
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Enalapril
  • Metalloendopeptidases