title: A vitamin D analog inhibits Th2 cytokine- and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis.
abstract: 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.
authors.affiliation: Department of Dermatology; Graduate School of Medicine; Osaka University ; Suita, Osaka, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Terao
authors.affiliation: Department of Dermatology; Graduate School of Medicine; Osaka University ; Suita, Osaka, Japan.
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Dermatology; Graduate School of Medicine; Osaka University ; Suita, Osaka, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Matsumura
authors.affiliation: Department of Dermatology; Graduate School of Medicine; Osaka University ; Suita, Osaka, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Yutani
authors.affiliation: Department of Dermatology; Graduate School of Medicine; Osaka University ; Suita, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.affiliation: Department of Dermatology; Graduate School of Medicine; Osaka University ; Suita, Osaka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
keywords: bleomycin; interleukin-4; interleukin-6; periostin; scleroderma; vitamin D