Transforming Growth Factor-β1 Induces a Mesenchyme-Like Cell Shape without Epithelial Polarization in Thyrocytes and Inhibits Thyroid Folliculogenesis in Collagen Gel Culture

Abstract

Transforming growth factor-beta1 (TGFbeta1) induces a mesenchyme-like cell shape in some epithelial cell types. To clarify the role of TGFbeta1 in the morphological regulation of thyrocytes, we performed collagen gel culture of porcine thyrocytes with serum-free medium. TGFbeta1-nontreated cells organized follicles. In contrast, the cells treated with 10 ng/ml TGFbeta1 became spindle shaped, i.e. they resembled mesenchymal fibroblasts, and did not form follicles. To characterize the spindle-shaped cells, we examined the fine structures and expression of thyroglobulin (Tg) and cytoskeletal proteins using electron microscopy, immunohistochemistry, and immunoblotting. TGFbeta1-nontreated cells had microvilli at the apical side facing follicle lumen and had basal lamina at the basal side in contact with collagen gel. TGFbeta1-treated cells showed both microvilli and basal lamina at the basal side. TGFbeta1-nontreated cells expressed Tg, whereas TGFbeta1-treated cells showed no expression. TGFbeta1-nontreated cells barely expressed vimentin, but they expressed enough cytokeratin. TGFbeta1-treated cells extensively displayed vimentin along with the change in shape to become spindle-like and retained a decreased expression of cytokeratin. TSH (10 mU/ml) did not essentially influence any TGFbeta1 effects on the cells. These results indicate that TGFbeta1 induces a mesenchyme-like cell shape accompanied by cytoskeletal molecular change and the loss of both epithelial polarization and a function in thyrocytes, and that it results in inhibiting thyroid folliculogenesis with or without TSH.