Tanshinone IIA ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-β–dependent epithelial to mesenchymal transition

BackgroundEpithelial to mesenchymal transition (EMT) of alveolar epithelial cells occurs in lung fibrotic diseases. Tanshinone ⅡA (Tan ⅡA) has been reported to exert anti-inflammatory effects in pulmonary fibrosis. Nonetheless, whether Tan ⅡA affects lung fibrosis-related EMT remains unknown and requires for further investigations.Materials and methodsA single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg body weight) was performed to induce pulmonary fibrosis in Sprague–Dawley rats. Rats receiving an instillation of equivoluminal normal saline served as controls. Then, these rats were given a daily intraperitoneal administration of Tan ⅡA (15 mg/kg body weight) for 28 d before sacrifice. In vitro, recombinant transforming growth factor-beta 1 (TGF-β1; 10 ng/mL) was used to treat human alveolar epithelial A549 cells for 48 h. Tan ⅡA (10 μM) or control DMSO was used to pretreat cells for 2 h before TGF-β1 stimulation. Rat lung tissue samples and A549 cells were then subjected to further assessments.ResultsTan ⅡA was noted to alleviate BLM–induced pulmonary collagen deposition and macrophage infiltration in rats. Epithelial-cadherin expression was decreased after BLM stimulation, whereas α-smooth muscle actin, fibronectin, and vimentin were increased. These expression alterations were partially reversed by Tan ⅡA. Moreover, Tan ⅡA suppressed BLM-induced increases in TGF-β1, phosphorylated Smad-2, and -3 in rats. Additionally, pretreatment of Tan ⅡA inhibited TGF-β1–triggered EMT, reduced collagen Ⅰ production, and blocked TGF-β signal transduction in A549 cells.ConclusionsOur research suggests that Tan ⅡA mitigates BLM–induced pulmonary fibrosis and suppresses TGF-β–dependent EMT of lung alveolar epithelial cells.