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

Abstract

& Ichiro Katayama (2015) A vitamin D analog inhibits Th2 cytokine-and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis, Dermato-Endocrinology, 7:1, e1010983, DOI: 10.1080DOI: 10. /19381980.2015 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 ), was applied to dermal fibroblasts and POSTN expression was measured. The effect of OCT on Th2 cytokine-and TGFb-induced POTSN and Collagen 1 a 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 TGFb-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 TGFb-induced POSTN expression.

Periostin involved in the activated hepatic stellate cells-induced progression of residual hepatocellular carcinoma after sublethal heat treatment: its role and potential for therapeutic inhibition

“…Vitamin and its analogues have been shown to attenuate fibrosis and delay tumor progression through suppressing the activities of fibroblasts, stellate cells [ 33 – 35 ]. In scleroderma, the vitamin D analogue inhibits TGF β-induced POSTN expression to reduce fibrosis [ 49 ]. Another study has reported that calcipotriol is capable of inhibiting POSTN expression in pancreatic ductal adenocarcinoma [ 33 ].…”

Evaluation of serum Vitamin D levels in patients with systemic sclerosis and healthy controls: Results of a pilot study

“…[ 25 ] Although topical vitamin D analog was found useful for localized scleroderma (morphoea), administration of cholecalciferol and/alfacalcidiol (2 mcg/d) has shown no effect or determined improvement in SSc symptoms. [ 26 27 28 ] It is possible that vitamin D deficiency perhaps plays some role in the subsequent development of a well-defined variant from undifferentiated connective tissue disease.…”

Comparative Proteomic Analysis of Bleomycin-induced Pulmonary Fibrosis Based on Isobaric Tag for Quantitation

“…In PF, the ECM receptor expression is increased in interstitial cells, leading to the proliferation and differentiation of interstitial lung cells via signal transduction after ligandreceptor binding, further promoting the synthesis and secretion of fibronectin and collagen. 22,23 The KEGG pathway enrichment revealed accumulation of a large number of DEPs between the model and the control groups in the renin-angiotensin system. Angiotensin II upregulates the expression of cytokine transforming growth factor-β, stimulates fibroblast proliferation, transforms fibroblasts to myofibroblasts and extracellular matrix deposition, resulting in fibrosis.…”