Transforming growth factor-beta1 induces a mesenchyme-like cell shape without epithelial polarization in thyrocytes and inhibits thyroid folliculogenesis in collagen gel culture.
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.
Toda
S
S
Department of Pathology, Saga Medical School, Japan. toda-s@post.saga-med.ac.jp
Matsumura
S
S
Fujitani
N
N
Nishimura
T
T
Yonemitsu
N
N
Sugihara
H
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D005782:Gels; D007633:Keratins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology*; D008854:Microscopy, Electron; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013552:Swine; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism
D005782:Gels; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014746:Vimentin; D007633:Keratins; D003094:Collagen; D013954:Thyroglobulin