Decreased expression of α2β1 integrin in scleroderma fibroblasts

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Abstract
Systemic scleroderma (SSc) is a complex connective tissue disorder of unknown etiology. In early stages of the disease, fibroblasts are activated to produce large amounts of collagen with subsequent fibrosis. Collagen metabolism of fibroblasts is modulated by their contact with the extracellular matrix (ECM), which involves distinct receptors on the cell surface, mainly belonging to the integrins. We investigated the expression of collagen receptor alpha 2 beta 1 in SSc and normal fibroblasts, since this receptor has been shown to be utilized by fibroblasts for adhesion to and reorganization of collagen I. 9 strains of scleroderma fibroblasts grown as monolayer cultures were first analyzed with respect to their collagen I expression. 6 of these strains were similar to controls "low" producers) and 3 strains showed up to 2-3 x higher levels of collage I mRNA expression ("high" producers). Northern hybridization using a cDNA probe specific for the alpha 2 integrin subunit revealed a decrease of the corresponding mRNA in SSc fibroblasts as compared to controls (75% versus 100%). "High" collagen producing cell strains displayed the lowest values for alpha 2 integrin mRNA. The decrease of alpha 2 integrin subunit expression at the mRNA level in selected fibroblasts was further substantiated by radioimmunoprecipitation using specific mAbs directed against alpha 2 integrin subunit. No significant changes in beta 1 integrin expression could be observed - neither at mRNA nor at the protein level. Our data indicate a correlation between excessive synthesis of collagen and low levels of alpha 2 integrin subunit expression in SSc fibroblasts. Further experiments should clarify whether this observation is a phenomenon specific for scleroderma or whether it reflects an "activated" state of fibroblasts.