9,13-di-cis-Retinoic acid induces the production of tPA and activation of latent TGF-beta via RAR alpha in a human liver stellate cell line, LI90.
We studied the mechanism by which 9,13-di-cis-retinoic acid (9,13dcRA), a novel and endogenous stereoisomer of all-trans-RA, induces TGF-beta formation in a human liver stellate cell line, LI90. 9,13dcRA induced the expression of RAR alpha and RARbeta, enhanced the production of tissue-type plasminogen activator (tPA), thereby, surface plasmin levels, and induced the activation of latent TGF-beta. Similar effects were obtained with RAR alpha-selective retinoid, but not with RARbeta- or RARgamma-selective retinoid, and the induction was inhibited by RAR alpha-selective antagonist. These results suggest that 9,13dcRA up-regulates tPA expression, resulting in the formation of TGF-beta by LI90 cells, at least in part, via induction and activation of RAR alpha.
Imai
S
S
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Okuno
M
M
Moriwaki
H
H
Muto
Y
Y
Murakami
K
K
Shudo
K
K
Suzuki
Y
Y
Kojima
S
S
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
C000607071:RARA protein, human; D012333:RNA, Messenger; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D016212:Transforming Growth Factor beta; C105492:9,13-retinoic acid; D014212:Tretinoin; D010959:Tissue Plasminogen Activator