TGF-BETA RECEPTORS ARE DIMINISHED AFTER RETINOID EXPOSURE IN RAT-LIVER EPITHELIAL-CELLS

When rat liver epithelial cells were exposed to retinoic acid or retin ol for 24 hr, the levels of transforming growth factor-beta (TGF-beta) receptors were reduced in a dose-dependent way. The decrease appeared after 12 hr of incubation with the retinoids and binding levels remai ned low until 24 hr after the removal of the molecules. Retinoid treat ment induced a fourfold enhancement of transglutaminase (TGase) activi ty in the cell membranes, and cystamine, an inhibitor of TGase, preven ted the decrease of the receptors. Neutralization of TGF-beta by a mon oclonal antibody did not suppress the decrease of the binding levels, indicating that decreased TGF-beta binding capacity was not due merely to the internalization of ligand-bound receptors promoted by a st;mul ation of TGF-beta synthesis. Thus, retinoid treatment resulted in an i ntense disappearance of the functional receptors from the membranes th at seemed to be mediated by increased TGase activity. This phenomenon can represent a strong signal attenuation for TGF-beta following retin oid exposure. (C) 1996 Wiley-Liss, Inc.