Upregulation of MMP-2 by all-trans retinoic acid is mediated by TGF-beta 1in cultured rat mesangial cell

Citation
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
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
FIBRINOLYSIS & PROTEOLYSIS
ISSN journal
1369-0191 → ACNP
Volume
14
Issue
4
Year of publication
2000
Pages
235 - 241
Database
ISI
SICI code
1369-0191(200007)14:4<235:UOMBAR>2.0.ZU;2-Y
Abstract
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.