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

FEBS Lett. 1997 Jul 7;411(1):102-6. doi: 10.1016/s0014-5793(97)00673-x.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Humans
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • RNA, Messenger
  • Rats
  • Receptors, Retinoic Acid / agonists
  • Receptors, Retinoic Acid / antagonists & inhibitors
  • Receptors, Retinoic Acid / biosynthesis
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Retinoic Acid Receptor alpha
  • Tissue Plasminogen Activator / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Tretinoin / analogs & derivatives*
  • Tretinoin / pharmacology


  • RARA protein, human
  • RNA, Messenger
  • Rara protein, rat
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Transforming Growth Factor beta
  • 9,13-retinoic acid
  • Tretinoin
  • Tissue Plasminogen Activator