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Regulation of human mesangial cell collagen expression by transforming growth factor-β1

1998; American Physical Society; Volume: 275; Issue: 3 Linguagem: Inglês

10.1152/ajprenal.1998.275.3.f458

1931-857X

Anne-Christine Poncelet, H. William Schnaper,

Hemostasis and retained surgical items

Transforming growth factor (TGF)-β1 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-β1 on collagen expression by human mesangial cells. TGF-β1 induced increased α 1 (I), α 1 (III), and α 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 α 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-β1 actions on collagen turnover may be either immediate or mediated through synthesis of regulatory molecules.