Influence of transforming growth factor beta 1 (TGF-beta 1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis

Transforming growth factor beta 1 (TGF-beta 1) is a secreted polypeptide th at is thought to play a major role in the regulation of folliculogenesis an d differentiation of thyroid cells. On porcine thyroid follicular cells cul tured on plastic substratum, TGF-beta 1, in a concentration-dependent way, promoted the disruption of follicles, cell spreading, migration and conflue ncy by a mechanism that did not involve cell proliferation. TGF-beta 1 stro ngly activated the production of thrombospondin-1 and alpha(v)beta 3 integr in in a concentration-dependent manner whereas the expression of thyroglobu lin was unaffected. Anisomycin, an inhibitor of protein synthesis, inhibite d the effect of TGP-beta 1 on cell organization. Thrombospondin-1 reproduce d the effect of TGF-beta 1, In the presence of thrombospondin-1 cells did n ot organize in follicle-like structures but, in contrast, spreaded and reac hed confluency independently of cell proliferation. This effect is suppress ed by an RGD-containing peptide. The adhesive properties of thrombospondin- 1 for thyroid cells were shown to be mediated by both the aminoterminal hep arin-binding domain and the RGD domain of thrombospondin-1. Adhesion was sh own to involve alpha(v)beta 3 integrin. The results show that TGF-beta 1 ex erted an influence upon function and behaviour of follicle cells partly med iated by the synthesis of thrombospondin-1 and of its receptor alpha(v)beta 3 integrin.