Expression of connective tissue growth factor in human thyroid tissue
QD Nguyen1, MA Buchanan1, JC Watkinson2 & MC Eggo1
Connective tissue growth factor (CTGF aka CCN2), is known to be up-regulated by transforming growth factor beta (TGF beta) and plays important roles in cell cycle control, growth, differentiation, cell adhesion, migration, angiogenesis and ECM production. CTGF is overexpressed in fibrotic disease e.g in kidney, lung, heart as well as in tumours. We have examined expression of CTGF in thyroid tissue because TGF beta is known be an autocrine factor, regulated by iodide. Immunohistochemical staining of CTGF in human thyroid tissue sections showed expression in thyroid follicular cells, connective tissue and blood vessels. Using a thyroid endothelial cell line, a strain of human thyroid fibroblasts and primary cultures of human thyroid follicular cells, we examined expression of CTGF and its receptor (low density lipoprotein receptor-related protein, LRP) by RT-PCR. Expression of both CTGF and LRP mRNA was found in all cell types. In addition we found CTGF mRNA in human thyroid cell lines derived from an anaplastic carcinoma (ARO) and a follicular carcinoma (FTC133). Immunofluorescence staining of these cell cultures showed strong expression of CTGF in the thyroid cell lines, particularly ARO cells, in fibroblasts and particularly in endothelial cells. There was no expression in the nuclei of non-dividing cells and the immunofluorescence was located in punctuate vesicles in the cytoplasm. There was a marked increase in endothelial cell expression of CTGF following 24 hour treatment with TGF beta (10 ng per ml). Other growth factors (FGF, EGF and VEGF) had no demonstrable effect on CTGF expression in endothelial cells or fibroblasts. Interestingly, CTGF expression was much higher during mitosis. This was particularly true for endothelial cells when the staining in mitotic nuclei and centrioles was exceptionally strong. The production of CTGF in thyroid tissue may play a role in thyroid growth.