BACKGROUND: Wnt/β-catenin signaling pathway has been shown to play an important role in the occurrence and development of systemic sclerosis, but the whether inhibiting Wnt/β-catenin can improve sclerosis is little reported.
OBJECTIVE: To explore the effect of inhibition of Wnt/β-catenin signaling pathway on skin tissue fibrosis and epithelial-mesenchymal transition in mice with scleroderma.
METHODS: Twenty-four BALB/c female mice were provided by Changsha Tianqin Biotechnology Co., Ltd., and the study was approved by the Experimental Animal Ethics Committee of University of South China. The mice were randomly divided into three groups: control group, model group and intervention group. Bleomycin was injected into the dorsal area of mice to establish the model of scleroderma. The control mice were subcutaneously injected with normal saline; the model mice were subcutaneously injected with 500 mg/L bleomycin, Mice of the intervention group were subcutaneously injected with 500 mg/L bleomycin and intraperitoneally injected with 5 mg/kg IGC-001 (Wnt/β-catenin signaling pathway inhibitor) at the same time, once daily, for 4 consecutive weeks. All mice were decapitated and the dorsal area skin of injection region was collected. Hematoxylin-eosin staining and Masson staining were used to observe the pathological changes of skin lesions, collagen fiber distribution and dermal thickness. The content of hydroxyproline in skin tissues was detected by hydrolysis method. The protein expression levels of β-catenin, type I collagen, fibronectin, α- smooth muscle actin, E-cadherin, vimentin and N-cadherin in skin tissues were detected by western blot assay.
RESULTS AND CONCLUSION: (1) After 4 weeks of continuous subcutaneous injection of bleomycin, the dermal thickness and collagen fibers in the skin tissues of model mice were significantly increased, while that in the intervention group were significantly decreased. (2) Compared with the control group, the hydroxyproline content and the protein expression levels of type I collagen, fibronectin, α-smooth muscle actin, vimentin, N-cadherin and β-catenin were significantly increased in the skin tissues of model group (all P < 0.05), and the protein expression of E-cadherin protein was significantly decreased (P < 0.05). Compared with the model group, the hydroxyproline content and the protein expression levels of type I collagen, fibronectin, α-smooth muscle actin, vimentin, N-cadherin were significantly decreased (P < 0.05), the protein expression level of E-cadherin protein was significantly increased (P < 0.05), while there was no significant change in the expression of β-catenin (P > 0.05). (3) To conclude, inhibition of Wnt/β-catenin signaling pathway may improve skin fibrosis in mice with scleroderma, and its mechanism may be related to inhibition of epithelial-mesenchymal transition in skin tissue.