Regulation of human mesangial cell collagen expression by transforming growth factor-beta1

Am J Physiol. 1998 Sep;275(3):F458-66. doi: 10.1152/ajprenal.1998.275.3.F458.

Abstract

Transforming growth factor (TGF)-beta1 has been implicated in glomerular extracellular matrix accumulation. Since the spectrum and mechanism of changes in collagen turnover have not been fully characterized, we evaluated effects of TGF-beta1 on collagen expression by human mesangial cells. TGF-beta1 induced increased alpha1(I), alpha1(III), and alpha1(IV) collagen mRNA expression. Greater mRNA expression of matrix metalloproteinase (MMP)-2 was compensated by increased tissue inhibitor of metalloproteinases (TIMP)-2 mRNA. There was no change in TIMP-1 or membrane-type MMP mRNA expression, whereas MMP-1 mRNA decreased. Types I and IV collagen protein accumulated in both the cell layer and medium. Changes in collagen mRNA and protein occurred within 4 and 8 h, respectively. MMP-2 and TIMP-1 and -2 activities showed little change. Cycloheximide markedly decreased collagen detection within 4 h and reversed late, but not early, changes in alpha1(I) collagen mRNA. In this system, increased synthesis may be more significant than degradation for collagen accumulation, but collagen is short-lived in culture. Diverse TGF-beta1 actions on collagen turnover may be either immediate or mediated through synthesis of regulatory molecules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Collagen / genetics*
  • Cycloheximide / pharmacology
  • Extracellular Matrix / metabolism
  • Gelatinases / genetics
  • Gelatinases / metabolism
  • Gene Expression Regulation*
  • Glomerular Mesangium / metabolism*
  • Humans
  • Kinetics
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta
  • Tissue Inhibitor of Metalloproteinase-2
  • Collagen
  • Cycloheximide
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2