Uchida Hiroko, Kuroki Motomu, Shitama Tomomi, Hayashi Hideyuki, Kuroki Masahide
Department of Ophthalmology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Curr Eye Res. 2008 Feb;33(2):199-203. doi: 10.1080/02713680701852090.
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.
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.
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.
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.
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。
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。
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。
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。
