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1
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60611
Transforming
growth factor (TGF)-
1 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-1 on collagen expression by human mesangial
cells. TGF-1 induced increased
1(I),
1(III), and
1(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 1(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-1 actions on collagen turnover
may be either immediate or mediated through synthesis of regulatory
molecules.
kidney; extracellular matrix; growth factor; collagen
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