Abnormal gene expression of matrix metalloproteinases and their inhibitor in glomeruli from diabetic rats

Ren Physiol Biochem. Nov-Dec 1994;17(6):316-25. doi: 10.1159/000173864.

Abstract

The steady state levels of mRNA encoding for metalloproteinase (MMP)-1, -2, -3, and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 were examined in glomeruli at 4, 12, and 24 weeks after the injection of streptozocin (STZ) in rats. The mRNA levels for MMP-1 and MMP-3 decreased with age in STZ-induced diabetes. At 24 weeks after STZ injection, 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 when compared with control rats. In contrast, mRNA levels for TIMP-1 increased significantly with age in the diabetic glomeruli and reached an 8-fold (p < 0.01) increased at 24 weeks after STZ injection. mRNA levels for MMP-2 were not altered in glomeruli from diabetic and control rats throughout the experimental period, whereas those for MMP-9 were not detected in glomeruli from either group of rats. Insulin treatment partially ameliorated the decrease in mRNA levels for MMP-1 and MMP-3 and the increase in those for TIMP-1 in the glomeruli of diabetic rats. These data indicate that abnormal gene regulation of MMPs and TIMP-1 in the glomeruli of diabetic rats may contribute to the progression of glomerular lesions and that hyperglycemia or insulin deficiency may be associated with abnormal MMPs and TIMP-1 gene regulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / physiopathology
  • Extracellular Matrix / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Insulin / pharmacology
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / physiopathology
  • Male
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Inhibitor of Metalloproteinases

Substances

  • Glycoproteins
  • Insulin
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Metalloendopeptidases