A vitamin D analog inhibits Th2 cytokine- and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis

摘要

Scleroderma is an autoimmune disease characterized by extracellular matrix deposition and inflammation. Topical vitamin D analogs have been reported as effective treatments for scleroderma. We previously reported that a matricellular protein, periostin (POSTN), contributes to pathogenesis of scleroderma as POSTN knockout mice were resistant to bleomycin (BLM)-induced scleroderma. We investigated whether a vitamin D analog affects the expression of POSTN in dermal fibroblasts and in a BLM-induced scleroderma model. The vitamin D analog, maxacalcitol (22-oxacalcitriol [OCT]), was applied to dermal fibroblasts and POSTN expression was measured. The effect of OCT on Th2 cytokine- and TGFβ-induced POTSN and Collagen 1 α 1 (Col1A1) expression was also assessed. In vivo, OCT was administered to BLM-induced scleroderma model and outcomes were determined by dermal thickness, collagen density and POSTN expression. Treatment with OCT significantly decreased POSTN expression in dermal fibroblasts. Th2 cytokine- and TGFβ-induced expression of POSTN and Col1A1 was also suppressed by OCT. In vivo, OCT administration decreased the density of collagen bundles and POSTN expression in a BLM-induced scleroderma model. In addition to the previously reported immunosuppressive effect, the vitamin D analog OCT might be effective to treat scleroderma, in part through inhibition of Th2 cytokine- and TGFβ-induced POSTN expression.