Paricalcitol Inhibits Wnt/β-Catenin Signaling Pathway and Ameliorates Dermal Fibrosis in Bleomycin Induced Scleroderma Model
Nevzat GÖZEL1, Fikret DURAN1, Ahmet YILDIRIM2, Servet YOLBAŞ2, Ebru ÖNALAN3, İbrahim Hanifi ÖZERCAN4, Süleyman Serdar KOCA2
1Department of Internal Medicine, Medical Faculty of Fırat University, Elazığ, Turkey
2Department of Rheumatology, Medical Faculty of Fırat University, Elazığ, Turkey
3Department of Medical Biology, Medical Faculty of Fırat University, Elazığ, Turkey
4Department of Pathology, Medical Faculty of Fırat University, Elazığ, Turkey
Keywords: Dermal fibrosis; paricalcitol; scleroderma; Wnt/β-catenin pathway
Objectives: This study aims to determine the prophylactic and therapeutic efficacy of inhibition of Wnt/β-catenin signaling pathway with paricalcitol in an experimental scleroderma model created with bleomycin (BLM).
Materials and methods: Sixty female BALB/c mice (8-week old and weighing 25 g to 30 g) were divided into six groups as prophylactic-early [group 1 (control I)], sham I (group 2), paricalcitol I (group 3), therapeutic-late [group 4 (control II)], sham II (group 5), and paricalcitol II (group 6) groups. Subcutaneous BLM (100 μg/day) injections were used to induce dermal fibrosis and paricalcitol (0.3 μg/kg/day) was applied subcutaneously to BLM-injected mice during the first three weeks for preventive interventions and in the second three weeks for therapeutic interventions. Tissue samples were harvested for subsequent pathological and real-time polymerase chain reaction analysis. Tissue transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions were determined by real-time polymerase chain reaction.
Results: Repeated BLM applications increased the dermal inflammatory cell infiltration and dermal thickness, and led to dermal fibrosis, in both early and late stages. Similarly, transforming growth factor-beta 1, axin-1, and Wnt-2 expressions were significantly increased in the sham groups compared to the own control group (p<0.05 for all). Contrarily, prophylactic and therapeutic paricalcitol applications decreased the transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions compared to the own sham group (p<0.05 for all). In addition, the regressions in dermal necro-inflammation and dermal fibrosis on pathological views were also observed in the paricalcitol applied groups.
Conclusion: In this model, increased axin-1 and Wnt-2 messenger ribonucleic acid expressions suggest that Wnt/β-catenin pathway is active in dermal fibrosis.
Citation: Gözel N, Duran F, Yıldırım A, Yolbaş S, Önalan E, Özercan İH, et al. Paricalcitol Inhibits Wnt/β-Catenin Signaling Pathway and Ameliorates Dermal Fibrosis in Bleomycin Induced Scleroderma Model. Arch Rheumatol 2018;33(3):288-294. ￼
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
This study was supported by Firat University Scientific Research Projects Coordination Unit (FUBAP).