This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Toda, S. Articles by Sugihara, H. Search for Related Content PubMed PubMed Citation Articles by Toda, S. Articles by Sugihara, H.

Transforming Growth Factor-ß1 Induces a Mesenchyme-Like Cell Shape without Epithelial Polarization in Thyrocytes and Inhibits Thyroid Folliculogenesis in Collagen Gel Culture

Departments of Pathology (S.T., T.N., N.Y., H.S.) and Biochemistry (S.M.), Saga Medical School, Saga 849; and the Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine (N.F.), Kurume 830, Japan

Address all correspondence and requests for reprints to: Dr. Shuji Toda, Department of Pathology, Saga Medical School, Nabeshima 5–1-1, Saga 849, Japan. E-mail: toda-s{at}post.saga-med.ac.jp

Transforming growth factor-ß1 (TGFß1) induces a mesenchyme-like cell shape in some epithelial cell types. To clarify the role of TGFß1 in the morphological regulation of thyrocytes, we performed collagen gel culture of porcine thyrocytes with serum-free medium. TGFß1-nontreated cells organized follicles. In contrast, the cells treated with 10 ng/ml TGFß1 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. TGFß1-nontreated cells had microvilli at the apical side facing follicle lumen and had basal lamina at the basal side in contact with collagen gel. TGFß1-treated cells showed both microvilli and basal lamina at the basal side. TGFß1-nontreated cells expressed Tg, whereas TGFß1-treated cells showed no expression. TGFß1-nontreated cells barely expressed vimentin, but they expressed enough cytokeratin. TGFß1-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 TGFß1 effects on the cells. These results indicate that TGFß1 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.

This article has been cited by other articles:

				E. Sonoda, S. Aoki, K. Uchihashi, H. Soejima, S. Kanaji, K. Izuhara, S. Satoh, N. Fujitani, H. Sugihara, and S. Toda A New Organotypic Culture of Adipose Tissue Fragments Maintains Viable Mature Adipocytes for a Long Term, Together with Development of Immature Adipocytes and Mesenchymal Stem Cell-Like Cells Endocrinology, October 1, 2008; 149(10): 4794 - 4798. [Abstract] [Full Text] [PDF]

				M. Grande, A. Franzen, J.-O. Karlsson, L. E. Ericson, N.-E. Heldin, and M. Nilsson Transforming growth factor-{beta} and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes J. Cell Sci., November 15, 2002; 115(22): 4227 - 4236. [Abstract] [Full Text] [PDF]

				N. Auersperg, A. S. T. Wong, K.-C. Choi, S. K. Kang, and P. C. K. Leung Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology Endocr. Rev., April 1, 2001; 22(2): 255 - 288. [Abstract] [Full Text]

				K. Chen, Y. Wei, G. C. Sharp, and H. Braley-Mullen Characterization of thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis J. Leukoc. Biol., December 1, 2000; 68(6): 828 - 835. [Abstract] [Full Text]

				H. Tonoli, V. Flachon, C. Audebet, A. Calle, T. Jarry-Guichard, M. Statuto, B. Rousset, and Y. Munari-Silem Formation of Three-Dimensional Thyroid Follicle-Like Structures by Polarized FRT Cells Made Communication Competent by Transfection and Stable Expression of the Connexin-32 Gene Endocrinology, April 1, 2000; 141(4): 1403 - 1413. [Abstract] [Full Text] [PDF]

				A. Franzén, E. Piek, B. Westermark, P. ten Dijke, and N.-E. Heldin Expression of Transforming Growth Factor-{beta}1, Activin A, and Their Receptors in Thyroid Follicle Cells: Negative Regulation of Thyrocyte Growth and Function Endocrinology, September 1, 1999; 140(9): 4300 - 4310. [Abstract] [Full Text]

				R. Montesano, J. V. Soriano, G. Hosseini, M. S. Pepper, and H. Schramek Constitutively Active Mitogen-activated Protein Kinase Kinase MEK1 Disrupts Morphogenesis and Induces an Invasive Phenotype in Madin-Darby Canine Kidney Epithelial Cells Cell Growth Differ., May 1, 1999; 10(5): 317 - 332. [Abstract] [Full Text]

				S. Yamada, S. Toda, T. Shin, and H. Sugihara Effects of Stromal Fibroblasts and Fat Cells and an Environmental Factor Air Exposure on Invasion of Laryngeal Carcinoma (HEp-2) Cells in a Collagen Gel Invasion Assay System Arch Otolaryngol Head Neck Surg, April 1, 1999; 125(4): 424 - 431. [Abstract] [Full Text] [PDF]

				D Claisse, I Martiny, B Chaqour, Y Wegrowski, E Petitfrere, C Schneider, B Haye, and G Bellon Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis J. Cell Sci., January 5, 1999; 112(9): 1405 - 1416. [Abstract] [PDF]