Regulation of human mesangial cell collagen expression by
transforming growth factor-[beta]1.
Poncelet, Anne-Christine, and H. William Schnaper.
Department of Pediatrics, Northwestern University Medical School,
Chicago, IL 60611, USA
APStracts 5:0106F, 1998.
Transforming growth factor (TGF)-[beta]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-[beta]1 on collagen
expression by human mesangial cells. TGF-[beta]1 induced increased
[alpha]1(I), [alpha]1(III) and [alpha]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, while MMP-1 mRNA decreased. Type 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/-2 activities showed little change. Cycloheximide
markedly decreased collagen detection within 4 h and reversed late,
but not early, changes in [alpha]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-[beta]1 actions on collagen turnover may be either
immediate or mediated through synthesis of regulatory molecules.
Received 16 January 1998; accepted in final form 8 June 1998.
APS Manuscript Number F13-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 16 June 1998