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

FEBS Letters

Kojima, Soichi⁴  Shudo, Koichi³  Suzuki, Yasuhiro⁴  Moriwaki, Hisataka²  Imai, Shoko²  Murakami, Kazuhiro¹  Okuno, Masataka²  Muto, Yasutoshi² 

[1] First Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980, Japan;First Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan;Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan;Laboratory of Gene Technology and Safety, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Koyadai, Tsukuba, Ibaraki 305, Japan

关键词: 9;    13-di-cis-Retinoic acid;    RARα;    tPA;    TGF-β;    Proteolytic activation;    Liver stellate cell;    GAPDH;    glyceraldehyde-3-phosphate dehydrogenase;    RA;    retinoic acid;    9;    13dcRA;    9;    13-di-cis-retinoic acid;    RAR;    retinoic acid receptor;    SC;    stellate cell;    TGF-β;    transforming growth factor-β;    tPA;    tissue-type plasminogen activator;   

DOI  :  10.1016/S0014-5793(97)00673-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown