Danshensu alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast-to-myofibroblast transition via the MEK/ERK signaling pathway

Abstract

Pulmonary fibrosis (PF) is a chronic pulmonary interstitial disease, and its pathological process is closely related to fibroblast-myofibroblast differentiation. Danshensu (DSS) has been reported to exert an anti-fibrotic effect in heart and liver. However, it is unknown whether DSS has an equally anti-fibrotic effect on lungs. To evaluate the effect of DSS on PF and demonstrate its possible molecular mechanisms, we established an <i>in vitro</i> model on TGF-β1 (5 ng/mL)-stimulated NIH3T3 cells and <i>in vivo</i> model on bleomycin (BLM) (5 mg/kg)-induced PF mice. <i>In vitro</i>, our results revealed that 50 μM DSS effectively inhibited the fibroblast proliferation, migration and differentiation into myofibroblast. <i>In vivo</i>, our results showed that DSS (28 and 56 mg/kg) reduced damaged lung structures, infiltrated inflammatory cells and accumulated areas of collagen deposition. Moreover, we showed that DSS decreased the fibroblast-specific protein 1 (FSP-1) - and α-SMA-positive areas. Meanwhile, we indicated that DSS reduced the expression of TGF-β1, α-SMA and COL-I in the lung tissues of mice. To further explore the mechanism of DSS on alleviating PF, we detected the MEK/ERK signaling pathway. Our results showed that DSS reduced the phosphorylation of MEK1/2 and ERK1/2, indicating that DSS might inhibit the MEK/ERK signaling pathway. Taken together, these results demonstrated that DSS could suppress lung fibroblast proliferation, migration and differentiation to myofibroblasts, possibly through suppressing the MEK/ERK signaling pathway, which suggested that DSS might be a potential therapeutic drug for PF treatment.