title: Tanshinone IIA attenuates epithelial-mesenchymal transition to inhibit the tracheal narrowing.
abstract: This 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.
  
  
  
  Human 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.
  
  
  
  In 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.
  
  
  
  Our research suggests that TIIA reduces tracheal narrowing after tracheal transplantation by suppressing TGF-β1-dependent EMT.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Respiratory Medicine, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China. Electronic address: yanxiaolong@fmmu.edu.cn.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China. Electronic address: lxffmmu@163.com.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007263:Infusions, Parenteral; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000378:metabolism / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology / Q000637:transplantation*; D014135:Tracheal Stenosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010616:Phenanthrenes; D020011:Protective Agents; D053773:Transforming Growth Factor beta1; C024894:tanshinone II A sodium sulfonate
keywords: Epithelial to mesenchymal transition; Tanshinone II a; Tracheal stenosis; Tracheal transplantation