视黄酸通过上调视网膜色素上皮细胞中血小板反应蛋白-1激活转化生长因子-β1。
Activation of TGF-beta1 through up-regulation of TSP-1 by retinoic acid in retinal pigment epithelial cells.
作者信息
Uchida Hiroko, Kuroki Motomu, Shitama Tomomi, Hayashi Hideyuki, Kuroki Masahide
机构信息
Department of Ophthalmology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
出版信息
Curr Eye Res. 2008 Feb;33(2):199-203. doi: 10.1080/02713680701852090.
PURPOSE
Retinoic acid (RA) affects the activation of transforming growth factor-beta 1 (TGF-beta1) in a variety of cells. We have previously shown that thrombospondin-1 (TSP-1) expression in retinal pigment epithelial (RPE) cells is up-regulated by RA. Since TSP-1 activates TGF-beta1, we investigated whether RA stimulates the activation of TGF-beta1 through up-regulation of TSP-1 in RPE cells.
METHODS
Human RPE cells were cultured with RA or TSP-1. The active form of TGF-beta1 in the culture medium was measured by enzyme-linked immunosorbent assay.
RESULTS
The active form of TGF-beta1 was increased dose-dependently by RA or TSP-1. The activation of TGF-beta1 by RA was significantly hampered by an anti-TSP-1 antibody. Also, antibodies against integrins alphavbeta3 and alphavbeta5 inhibited the activation of TGF-beta1.
CONCLUSIONS
These findings suggest that, in RPE cells, RA increases the activation of TGF-beta1 via up-regulation of TSP-1, and integrins such as alphavbeta3 and alphavbeta5 are essential in this activation step.
目的
维甲酸（RA）可影响多种细胞中转化生长因子-β1（TGF-β1）的激活。我们之前已表明，视网膜色素上皮（RPE）细胞中血小板反应蛋白-1（TSP-1）的表达受RA上调。由于TSP-1可激活TGF-β1，我们研究了RA是否通过上调RPE细胞中的TSP-1来刺激TGF-β1的激活。
方法
将人RPE细胞与RA或TSP-1一起培养。通过酶联免疫吸附测定法测量培养基中TGF-β1的活性形式。
结果
RA或TSP-1可使TGF-β1的活性形式呈剂量依赖性增加。抗TSP-1抗体可显著抑制RA对TGF-β1的激活。此外，抗整合素αvβ3和αvβ5抗体也可抑制TGF-β1的激活。
结论
这些发现表明，在RPE细胞中，RA通过上调TSP-1增加TGF-β1的激活，而整合素如αvβ3和αvβ5在这一激活步骤中至关重要。
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