Imai S, Okuno M, Moriwaki H, Muto Y, Murakami K, Shudo K, Suzuki Y, Kojima S
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
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.
我们研究了9,13 - 二顺式视黄酸（9,13dcRA），一种全反式视黄酸的新型内源性立体异构体，在人肝星状细胞系LI90中诱导转化生长因子-β（TGF-β）形成的机制。9,13dcRA诱导视黄酸受体α（RARα）和视黄酸受体β（RARβ）的表达，增强组织型纤溶酶原激活物（tPA）的产生，从而提高表面纤溶酶水平，并诱导潜伏性TGF-β的激活。RARα选择性类视黄醇也获得了类似的效果，但RARβ或RARγ选择性类视黄醇则没有，并且这种诱导被RARα选择性拮抗剂抑制。这些结果表明，9,13dcRA上调tPA表达，导致LI90细胞至少部分通过诱导和激活RARα形成TGF-β。
