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Retinoids potentiate transforming growth factor‐β activity in bovine endothelial cells through up‐regulating the expression of transforming growth factor‐β receptors
Author(s) -
Yoshizawa Misako,
Miyazaki Hitoshi,
Kojima Soichi
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199809)176:3<565::aid-jcp13>3.0.co;2-z
Subject(s) - transforming growth factor , receptor , plasminogen activator , retinoic acid , plasmin , growth factor , cell growth , chemistry , plasminogen activator inhibitor 1 , endocrinology , medicine , activator (genetics) , biology , microbiology and biotechnology , cell culture , biochemistry , genetics , enzyme
Retinoic acid (RA) induces the activation of latent transforming growth factor‐β (TGF‐β) in bovine aortic endothelial cells (BAECs) via enhancement of cellular plasminogen activator (PA)/plasmin levels. The resultant TGF‐β 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‐β receptor types I and II, resulting in enhancement of TGF‐β activity in the cells. RA increased the numbers of high‐ and low‐affinity binding sites for 125 I‐TGF‐β1 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 μM 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‐β1 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‐β but also by stimulating TGF‐β receptor expression. This regulatory mechanism may sustain TGF‐β‐mediated regulation of EC function at a focal site where RA is acting. J. Cell. Physiol. 176:565–573, 1998. © 1998 Wiley‐Liss, Inc.