Retinoids potentiate transforming growth factor-β activity in bovine endothelial cells through up-regulating the expression of transforming growth factor-β receptors

✍ Scribed by Misako Yoshizawa; Hitoshi Miyazaki; Soichi Kojima

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 260 KB
• Volume: 176
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199809)176:3<565::aid-jcp13>3.0.co;2-z

✦ Synopsis

Retinoic acid (RA) induces the activation of latent transforming growth factor-b (TGF-b) in bovine aortic endothelial cells (BAECs) via enhancement of cellular plasminogen activator (PA)/plasmin levels. The resultant TGF-b suppresses the excessive fibrinolytic activity by decreasing PA expression and stimulating expression of the PA inhibitor, PA inhibitor-1 (PAI-1), and inhibits cell proliferation. Here, we report that, in this regulatory system, RA simultaneously up-regulates the expression of TGF-b receptor types I and II, resulting in enhancement of TGFb activity in the cells. RA increased the numbers of high-and low-affinity binding sites for 125 I-TGF-b1 2.1-fold and 1.5-fold, respectively, without alteration of their Kd values. Affinity labeling and Western and Northern blotting studies showed that, following RA treatment, surface levels of both type I and type II receptors increased due to augmentation in their mRNA levels. The effect was dose-and time-dependent. Treatment with 1 mM RA for 15 hr increased mRNA levels of type I and II receptor threefold and eightfold, respectively. Pretreatment of BAECs with either RA or retinol lowered the concentration of TGF-b1 required to suppress PA levels, to enhance PAI-1 levels, and to inhibit cell proliferation. Thus, retinoids may regulate cellular functions of BAECs not only by inducing the formation of active TGF-b but also by stimulating TGF-b receptor expression. This regulatory mechanism may sustain TGF-b-mediated regulation of EC function at a focal site where RA is acting.