Transforming growth factor beta-1 up-regulates clusterin synthesis in thyroid epithelial cells

Porcine epithelial cells in primary culture seeded on plastic substratum fo rm a monolayer containing pseudo-vesicles. When cultured in the presence of thyreotropin (TSH) thyrocytes adopted a follicular-like structure and form ed clusters, Transforming growth factor beta-1 (TGF beta(1)) induced a rapi d spreading of the TSH-treated cells only. At the same time, TGF beta(1) en hanced clusterin protein and mRNA expression. The increase of clusterin syn thesis was proportional to the TGF beta(1) concentration in the culture med ium. Tunicamycin abolished the up-regulation of whole clusterin synthesis a nd morphological changes. The activator protein-1 binding site partly direc ted the TGF beta(1)-stimulated clusterin expression. Phorbol ester caused r apid spreading of the cells with disappearance of vesicular and follicular structures. It decreased clusterin mRNA and protein expression, but increas ed M-r 45,000 protein secretion in both TSH-treated and nontreated cells. U p-regulation of clusterin expression may be a marker of TGF beta-mediated t hyrocyte dedifferentiation. (C) 1999 Academic Press.