Τόμος 26 (2012) – Τεύχος 2 – Άρθρο 1 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 26 (2012) – Issue 2 – Article 1- Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title The functional role of glycosaminoglycans in the pathophysiology of the thyroid gland and their putative role as prognostic, diagnostic and therapeutic agents in thyroid pathologies
Authors Eleni Memi, George Karakiulakis, Fani Goma and Eleni Papakonstantinou

Dept of Pharmacology, School of Medicine, Aristotle University, Thessaloniki GR 54124, Greece

Citation Memi, E., Karakiulakis, G., Goma, F., Papakonstantinou, E.: The functional role of glycosaminoglycans in the pathophysiology of the thyroid gland and their putative role as prognostic, diagnostic and therapeutic agents in thyroid pathologies, Epitheorese Klin. Farmakol. Farmakokinet. 26(2): 61-86 (2012)
Publication Date Accepted for publication (Final Version): April 10, 2013
Full Text Language English
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Keywords Thyroid pathologies, glycosaminoglycans, hyaluronic acid, dermatan sulfate, chondroitin sulfate, keratan sulfate, heparan sulfate, heparin, proteoglycans, perlecan, syndecan, versican, decorin, glypican, CD44
Other Terms review article
Summary Glycosaminoglycans are linear acidic polysaccharides, comprising hyaluronic acid, dermatan sulfate, chondroitin sulfate, keratan sulfate, heparin sulfate and heparin, which differ in their specific composition. These molecules are encountered in the extracellular matrix and play a major role in the development of tissues physiological properties. With the exception of hyaluronic acid, glycosaminoglycans are covalently linked to core proteins to form proteoglycans. Glycosaminoglycans and proteoglycans are involved in important biological events, such as cellular proliferation, adhesion, migration and differentiation. These molecules have also been shown to participate in the development of both neoplastic and hyperplastic, space occupying lesions. In the field of thyroidology, it has been shown that glycosaminoglycans, proteoglycans and related molecules play a major role in the development of both physiological properties and pathological conditions of the thyroid gland. Numerous studies, including our own, support the involvement of glycosaminoglycans and proteoglycans, such as perlecan, syndecan, versican, decorin, glypican and CD44, in the pathogenesis of hyperplastic and autoimmune lesions, benign neoplasms and malignancies. These molecules show distinct features in thyroid diseases, which may be helpful in understanding the complex behaviour of these diseases. Their value as biomarkers and therapeutic targets or vehicle components remains to be determined, but preliminary data are encouraging. Our own results were based on the investigation of tissue specimens dissected from thyroid glands of patients who underwent thyroidectomy for nodular goitre (n=42), thyroiditis Hashimoto (n=11), follicular adenoma (n=7) and papillary carcinoma (n=9). Total glycosaminoglycans were isolated from homogenized tissue specimens and they were characterized using glycosaminoglycans-degrading enzymes. In addition, a part of each specimen was elaborated for the extraction of total RNA and the expression of proteoglycans and enzymes metabolizing hyaluronic acid were tested by RT-PCR analysis. We found a statistically significant increase of dermatan sulfate and heparan sulfate in nodular goitre, which was not observed in the other thyroid pathologies examined in our study. Our results also showed a statistically significant increase of hyaluronic acid in papillary carcinoma, follicular adenoma and thyroiditis Hashimoto, which was associated with: a) increased expression of hyaluronic acid synthase (HAS)-2 and HAS-3 in all three diseases; b) decreased expression of both hyaluronidase (HYAL)-1 and HYAL-3 in papillary carcinoma and follicular adenoma and c) decreased expression of HYAL-3 in thyroiditis Hashimoto. Moreover, RT-PCR analysis demonstrated a statistically significant decrease of the expression of syndecan-1 in papillary carcinoma and follicular adenoma and a statistically significant increase of the expression of versican V1 in all thyroid diseases examined in our study. These finding may be proved to be useful for the differential diagnosis between benign and malignant thyroid nodules. This review summarizes currently available data regarding glycosaminoglycans and proteoglycans in relation to thyroid pathophysiology, which may be exploited for the development of novel prognostic, diagnostic and therapeutic strategies, easing the resolution of common clinical dilemmas in thyroid pathology.
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