The effectiveness of paricalcitol in bleomycin induced experimental scleroderma

For Scleroderma, it is thought that Signaling pathway of activated wingless-type MMTV integration site (Wnt)/β-catenin contributes to fibrotic process in the stage of transformation of fibroblasts into myofibroblasts and even transformation of non-fibroblastic cells to fibroblastic cells. Paricalcitol inhibits connection of T-cell factor (TCF-4) from transcription factors to the β-catenin as competitively through vitamin D receptor (VDR) and thus inhibits the activity of the Wnt/β-catenin signaling pathway. The aim of our study, in experimental scleroderma models created with BLM, is to determine prophylactic and therapeutic efficacy of inhibition of Wnt/β-catenin signaling pathway with paricalcitol which is synthetic vitamin D analog. 60 Balb/c female mice were taken to this study. 6 groups were formed as early stage groups (groups [Control group], II [placebo group] and III [paricalcitol group]) and late-stage groups (group IV [Control group], V [placebo group] VI [paricalcitol group]). Salin (PBS) which was buffered with phosphate everyday was applied from shaved region to the control group of mice (Group I) and (group IV) which BLM will not be applied to. 1mg BLM by dissolving it in 1 ml FTS as 100L (100g) dose was applied sc daily to mice in group of II and III along 3 weeks, in the group of V and VI along 6 weeks. In addition to BLM, Paricalcitol (0.3g / kg) was injected daily with sc route to third group mice first three week and to sixth group mice group from 21th day until the end of the working day. The first three groups at the end of the third week; the remaining groups at the end of six weeks, 24 hours after the last treatment, were sacrificed by decapitation. Tissue samples was collected for the histopathological and real-time polymerase chain reaction (RT-PCR) analysis. Tissue TGF-β1, axin-1 and Wnt-2 mRNA expression was determined by RT-PCR. As a result of repeated BLM subcutaneous implementation; in the early and late stage, an increase took place in the dermal inflammatory cell infiltration, dermal thickness dermal fibrosis. Similarly; TGF-β1, axin-1 and wnt-2 expression was significantly increased. In the Prophylactic and therapeutic applications of paricalcitol, TGF-β1, axin-1 and Wnt-2 mRNA expression decreased significantly. In addition, it was determined regression in dermal necro inflammation and dermal fibrosis as histopathological. In conclusion, in the BLM-induced dermal fibrosis model, increased AX-1 wnt-2 mRNA expressions supports that Wnt / β-catenin signaling pathway is active in dermal fibrosis. Moreover, paricalcitol has antifibrotic potential and this effect may be associated on Wnt / β-catenin signaling pathway. Key Words: Experimental scleroderma, Wnt/β-catenin signaling pathway, Paricalcitol