Expression of proteoglycans and glycosaminoglycans in angiofibroma and fibrous plaque skin lesions from patients with tuberous sclerosis.

Abstract

Tuberous sclerosis complex (TSC) is a disorder of cell lineage, migration, proliferation and differentiation, characterized by the development of widespread benign hamartomas, which are particularly evident in hamartomatous lesions of the skin. The aim of this study was to investigate differences in gene expression of certain proteoglycans (PGs) and to characterize glycosaminoglycans (GAGs) in tissue specimens of normal skin, fibrous plaques and angiofibromas from patients with TSC. The expression of PG mRNA was determined by semiquantitative RT-PCR analysis. Total GAGs were isolated from tissue specimens after lipid extraction and extensive digestion with Pronase and DNase and characterized by treatment with GAG-degrading enzymes followed by electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes. Normal skin specimens express versican, decorin and aggrecan and contain hyaluronic acid and dermatan sulphate. In angiofibroma specimens aggrecan is not expressed while versican splice variant with two EGF-like domains and decorin are downregulated. Furthermore, angiofibromas differ from normal skin in that they additionally contain keratan, heparan and chondroitin sulphates and do not contain dermatan sulphate. In fibrous plaque specimens gene expression of PGs was similar to that in normal skin, but with respect to GAGs, they contained a single acidic glycan population that did not share common structural features with known GAGs. The variations of the above ECM molecules between normal and TSC skin may be attributed to TSC-related mutations and, overall, support the TSC-associated pathological manifestations of cell migration, proliferation and differentiation.