Scorpion Venom Polypeptide Inhibits Pulmonary Epithelial-mesenchymal Transition in Systemic Sclerosis-interstitial Lung Disease Model Mice by Intervening TGF-β1/Smad Signaling Pathway

Abstract Objective Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease, and interstitial lung disease (ILD) is an important complication of SSc. The aim of this study was to investigate the effect of polypeptide extract of scorpion venom (PESV) on alleviating pulmonary epithelial-mesenchymal transition (EMT) in SSc-ILD mice and its possible mechanism. Methods C57/BL6 mice were injected with bleomycin to establish a SSc-ILD model. Different concentrations of PESV solution were administered, and dexamethasone was used as a positive control. Then the lung tissues of mice in each group were removed, and the pathological changes of mice in each group were observed using HE staining and Masson staining. TGF-β1 expression levels were detected by immunohistochemical. The expression of EMT-related proteins E-cadherin, collagenI, vimentin, N-cadherin, and α-SMA was detected by Western blot, and the expression of TGF-β1/Smad pathway-related proteins was also detected. The contents of inflammatory cytokines IL-6, TNF-α and TGF-β1 in serum and BALF were also measured by ELISA. Results Pathological analysis showed that PESV alleviated the SSc-ILD induced pulmonary inflammation and fibrosis. The results showed that after PESV treatment, the contents of inflammatory cytokines IL-6 and TNF-α were significantly lower than those in the model group. PESV could increase the expression of epithelial marker E-cadherin and reduce the expression of interstitial markers collagenI, vimentin, N-cadherin, and α-SMA. PESV can reduce the expression level of TGF-β1/Smad pathway-related proteins . Conclusion PESV can inhibit the EMT and relevant TGF-β1/Smad signaling pathway, to alleviate pulmonary inflammation and fibrosis, thus to play a protective effect against SSc-ILD.