Activation of TGF-β1 Through Up-Regulation of TSP-1 by Retinoic Acid in Retinal Pigment Epithelial Cells

Abstract

Purpose: Retinoic acid (RA) affects the activation of transforming growth factor-β 1 (TGF-β 1) 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-β 1, we investigated whether RA stimulates the activation of TGF-β 1 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-β 1 in the culture medium was measured by enzyme-linked immunosorbent assay. Results: The active form of TGF-β 1 was increased dose-dependently by RA or TSP-1. The activation of TGF-β 1 by RA was significantly hampered by an anti-TSP-1 antibody. Also, antibodies against integrins α vβ 3 and α vβ 5 inhibited the activation of TGF-β 1.Conclusions: These findings suggest that, in RPE cells, RA increases the activation of TGF-β 1 via up-regulation of TSP-1, and integrins such as α vβ 3 and α vβ 5 are essential in this activation step.

KEYWORDS:

• integrin
• retinal pigment epithelium
• retinoic acid
• thrombospondin-1
• transforming growth factor-β1