W. Lin et al., Upregulation of MMP-2 by all-trans retinoic acid is mediated by TGF-beta 1in cultured rat mesangial cell, FIBRINOL PR, 14(4), 2000, pp. 235-241
Matrix metalloproteinase-2 (MMP-2) degrades basement membrane collagen and
its abnormal expression is associated with glomerulonephritis and glomerulo
sclerosis. All-trans retinoic acid (ATRA) has been indicated as preventing
age-related glomerulosclerosis. The results of our study showed that ATRA u
pregulated expression of MMP-2 mRNA and secretion of MMP-2 proteins, and in
creased enzymatic activity of MMP-2 in cultured mesangial cell. In addition
, ATRA also caused a dose-dependent increase in the secretion of transformi
ng growth factor-beta (TGF-beta 1) peptides. Since TGF-beta 1 regulated the
expression of MMP-2 in mesangial cell, it is possible that TGF-beta 1 is i
nvolved in ATRA-induced MMP-2 expression. Using antisense TGF-beta 1 RNA st
rategy, antisense TGF-beta 1 construct almost completely blocked secretion
of active TGF-beta 1 peptides in the antisense-bearing transfectants. North
ern blot analysis showed that the transfectants treated with 10(-6)M ATRA f
or 72 h neither increased nor decreased the levels of MMP-2 messenger ribon
ucleic acid (mRNA). Moreover, addition of anti-TGF-beta 1 antibodies to mes
angial cell in the presence of 10(-6)M ATRA reduced ATRA-induced MMP-2 expr
ession dose dependently. These data suggest that TGF-beta 1 might be involv
ed in ATRA-induced MMP-2 expression. (C) 2000 Harcourt Publishers Ltd.