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Curr Eye Res. 2008 Feb;33(2):199-203. doi: 10.1080/02713680701852090.

Activation of TGF-beta1 through up-regulation of TSP-1 by retinoic acid in retinal pigment epithelial cells.

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  • 1Department of Ophthalmology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.



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.

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