Tanshinone IIA attenuates epithelial–mesenchymal transition to inhibit the tracheal narrowing

BackgroundThis study examines the effects of tanshinone IIA (TIIA) on epithelial–mesenchymal transition (EMT) in tracheal transplantation and the ability of TIIA to inhibit tracheal narrowing after tracheal transplantation. Mechanisms that may be involved in this process are also explored.MethodsHuman bronchial epithelial cells were treated in vitro with TGF-β1 for 72 h. The cells were pretreated with TIIA (40 μg/mL) or DMSO for 2 h before TGF-β1 stimulation. For the in vivo experiments, tracheas (5-6 rings) from Wistar rats were orthotopically transplanted into Sprague–Dawley rats. The experimental group received multiple infusions of sodium TIIA sulfonate (25 mg/kg, qd, intraperitoneally). The control group received infusions of the same volume of saline. Allografts were harvested at 3, 7, 10, 14, 35, and 90 d after transplantation and were examined for tracheal narrowing. Tracheal tissue samples and human bronchial epithelial cell were then subjected to further tests.ResultsIn the in vitro assay, epithelial cadherin expression was decreased after TGF-β1 stimulation, whereas α-smooth muscle actin and vimentin expression levels were increased. The expression levels of ZEB1 and Snail1 were also increased. These changes in expression were partially reversed by treatment with TIIA. In the in vivo assay, TIIA alleviated tracheal stenosis after tracheal allograft transplantation in rats and mitigated EMT by inhibiting the Smad signaling pathway and the expression of the transcription factors ZEB1 and Snail1.ConclusionsOur research suggests that TIIA reduces tracheal narrowing after tracheal transplantation by suppressing TGF-β1–dependent EMT.