Regulation of human mesangial cell collagen expression by transforming growth factor-beta1.
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.
Poncelet
A C
AC
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Schnaper
H W
HW
D015152:Blotting, Northern; D003094:Collagen / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D003513:Cycloheximide; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2