9,13‐di‐cis‐Retinoic acid induces the production of tPA and activation of latent TGF‐β via RARα in a human liver stellate cell line, LI90

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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‐β formation in a human liver stellate cell line, LI90. 9,13dcRA induced the expression of RARα and RARβ, enhanced the production of tissue‐type plasminogen activator (tPA), thereby, surface plasmin levels, and induced the activation of latent TGF‐β. Similar effects were obtained with RARα‐selective retinoid, but not with RARβ‐ or RARγ‐selective retinoid, and the induction was inhibited by RARα‐selective antagonist. These results suggest that 9,13dcRA up‐regulates tPA expression, resulting in the formation of TGF‐β by LI90 cells, at least in part, via induction and activation of RARα.

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