Activation of TGF-beta1 through up-regulation of TSP-1 by retinoic acid in retinal pigment epithelial cells.
OBJECTIVE
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.
Uchida
Hiroko
H
Department of Ophthalmology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. kuchida@aurora.ocn.ne.jp
Kuroki
Motomu
M
Shitama
Tomomi
T
Hayashi
Hideyuki
H
Kuroki
Masahide
M
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000502:physiology; D016023:Integrins / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000502:physiology; D019700:Thrombospondin 1 / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
D039302:Integrin alphaVbeta3; D016023:Integrins; D019030:Receptors, Vitronectin; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; C064660:integrin alphaVbeta5; D014212:Tretinoin