Decreased expression of alpha2 integrin in fibroblasts isolated from cyclosporin A- induced gingival overgrowth in rats.

Abstract

Cyclosporin A (CsA), an immunosuppressive agent, induces fibrous gingival overgrowth through reduction of collagen phagocytosis by fibroblasts. Distinct receptors are involved in the binding of collagen to fibroblasts in collagen phagocytosis, and alpha2beta1 integrin serves as a specific receptor for type I collagen on fibroblasts. To elucidate the role of alpha2beta1 integrin in CsA-induced gingival overgrowth, we investigated collagen phagocytosis and alpha2beta1 integrin expression in rat gingival fibroblasts. Fibroblats were isolated from gingiva of rats fed a powdered diet containing or lacking CsA for 30 d. Flow cytometric analysis were performed to measure the collagen phagocytosis and the alpha2 integrin expression in fibroblasts. Furthermore, total RNAs were isolated from fibroblasts, and the reverse transcriptase-polymerase chain reaction was employed to investigate the mRNA levels of alpha2 integrin. In vitro collagen phagocytosis assay revealed that CsA-treated and control fibroblasts contained a mean of 13.5% and 36.1% phagocytic cells, respectively. CsA-treated fibroblasts had 28% lower expression of alpha2 integrin than that of control. and mRNA expression of alpha2 integrin in CsA-treated fibroblasts was apparently lower than in the controls, but the mRNA expression of beta1 integrin was not affected. These findings suggest that one etiological factor of gingival overgrowth may be inhibition of collagen phagocytosis by reducing alpha2 integrin expression in gingival fibroblasts.