Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cells, Cultured
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Humans
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Liver / cytology
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Liver / drug effects
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Liver / metabolism*
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RNA, Messenger
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Rats
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Receptors, Retinoic Acid / agonists
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Receptors, Retinoic Acid / antagonists & inhibitors
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Receptors, Retinoic Acid / biosynthesis
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism*
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Retinoic Acid Receptor alpha
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Tissue Plasminogen Activator / biosynthesis*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
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Tretinoin / analogs & derivatives*
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Tretinoin / pharmacology
Substances
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RARA protein, human
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RNA, Messenger
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Rara protein, rat
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Receptors, Retinoic Acid
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Retinoic Acid Receptor alpha
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Transforming Growth Factor beta
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9,13-retinoic acid
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Tretinoin
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Tissue Plasminogen Activator