Huang Xun, Yan Xiaolong, Zhang Zhipei, Li Xiaofei
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
Otolaryngol Head Neck Surg. 2015 Jun;152(6):1068-74. doi: 10.1177/0194599815577102. Epub 2015 Mar 27.
The specific role and mechanism of epithelium in the progression of obliterative airway disease (OAD) after tracheal allotransplantation remain poorly understood. In this study, we used rat heterotopic tracheal transplantation to investigate the mechanism of epithelial cell seeding during the process of OAD.
Prospective, basic science.
Research laboratory.
In total, 120 Sprague Dawley (SD) rats and 90 Wistar rats were used. Tracheas from SD rats were implanted into SD rats (syngeneic, n = 30) or Wistar rats (allogeneic, n = 30), and SD rat tracheas (seeded with Wistar rat-derived epithelial cells 6 days after transplantation) were transplanted into Wistar rats (seeded allogeneic, n = 30). Grafts were harvested at 7, 14, or 30 days after transplantation for histologic, quantitative reverse transcriptional polymerase chain reaction or Western blot analyses.
Syngrafts retained normal histologic structures, while the corresponding allografts demonstrated less ciliated epithelia and more lumenal occlusion. Seeding of epithelial cells ameliorated the histologic changes, reduced the expression of epithelial to mesenchymal transition (EMT)-related transcriptional factors and mesenchymal markers, and dampened the expression of transforming growth factor β1 (TGF-β1) and phosphorylation of smad3.
Seeding of recipient epithelial cells inhibits the progression of OAD by attenuating EMT via TGF-β-Smad signaling in rat heterotopic tracheal allografts. Clinically, the injection of recipient-originated epithelial cells might provide new insights into the treatment for OAD after tracheal allotransplantation.
气管同种异体移植后上皮细胞在闭塞性气道疾病（OAD）进展中的具体作用和机制仍不清楚。在本研究中，我们采用大鼠异位气管移植来研究OAD过程中上皮细胞植入的机制。
前瞻性基础科学研究。
研究实验室。
共使用120只Sprague Dawley（SD）大鼠和90只Wistar大鼠。将SD大鼠的气管植入SD大鼠（同基因，n = 30）或Wistar大鼠（异基因，n = 30），并将移植6天后接种Wistar大鼠来源上皮细胞的SD大鼠气管移植到Wistar大鼠（接种异基因，n = 30）。在移植后7、14或30天采集移植物进行组织学、定量逆转录聚合酶链反应或蛋白质免疫印迹分析。
同基因移植物保留正常组织结构，而异基因移植物显示纤毛上皮减少，管腔阻塞增多。上皮细胞接种改善了组织学变化，降低了上皮-间质转化（EMT）相关转录因子和间质标志物的表达，并抑制了转化生长因子β1（TGF-β1）的表达和smad3的磷酸化。
受体上皮细胞接种通过减弱大鼠异位气管同种异体移植中TGF-β-Smad信号通路介导的EMT来抑制OAD进展。临床上，注射受体来源的上皮细胞可能为气管同种异体移植后OAD的治疗提供新的思路。
