Epithelial to mesenchymal transition in murine tracheal allotransplantation: an immunohistochemical observation.
Epithelial to mesenchymal transition in murine tracheal allotransplantation: an immunohistochemical observation.
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DOI：
10.1016/j.transproceed.2012.11.024
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发表时间：
2013-06
影响因子：
0.9
通讯作者：
Murakawa, T.
中科院分区：
文献类型：
--
作者：
Konoeda, C.;Koinuma, D.;Morishita, Y.;Sano, A.;Nagayama, K.;Motomura, N.;Kakimi, K.;Miyazono, K.;Nakajima, J.;Nicolis, M. R.;Murakawa, T.
上皮细胞异常修复是移植肺闭塞性细支气管炎（OB）气道重塑的重要环节。最近的实验数据表明，上皮细胞系和肺移植受体的人气道组织上皮间质转化（EMT）在OB中起着重要作用。本研究的目的是在动物模型中阐明EMT是否参与气道重塑。我们进行了BALB/c小鼠至C57 BL/6小鼠的原位气管移植，并以BALB/c小鼠至BALB/c小鼠的移植物作为对照。在预定的术后第2-12天以及第14天和第21天，人道处死5名同种异体和3名同系受体。使用苏木精-伊红（H&E）染色评价组织学。我们研究了特异性标志物的表达，包括上皮标志物E-钙粘蛋白、间充质标志物α-平滑肌肌动蛋白（SMA）和S100 A4以及EMT相关转录因子锌指E-box-binding homeobox 1（ZEB 1）。同种异体移植物的系列H&E染色的组织学评估显示显著的假复层呼吸道上皮伴上皮下炎性细胞浸润，以及剥脱和扁平上皮和上皮下纤维化。动态上皮改变早于上皮下纤维化。免疫组织化学评价表明出现了α-SMA阳性上皮细胞，在第7天最为突出。α-SMA阳性上皮细胞E-cadherin表达减弱。S100 A4也在上皮细胞中表达。在α-SMA表达的前几天，上皮细胞的细胞核中出现了ZEB 1。在显著的上皮下纤维化形成前几天，我们观察到上皮细胞中EMT相关转录因子和间充质标志物沿着上皮标志物表达的减弱，结果表明上皮细胞在上皮向间充质转化期间的气道重塑中发挥重要的纤维化作用。
Aberrant epithelial repair is a crucial event in the airway remodeling that characterizes obliterative bronchiolitis (OB) in transplanted lungs. Recent data from experiments using epithelial cell lines and human airway tissues from lung transplant recipients suggest that epithelial to mesenchymal transition (EMT) plays an important role in OB. The aim of this study was to clarify whether EMT is involved in airway remodeling in an animal model. We performed orthotopic tracheal transplantation from BALB/c to C57BL/6 mice with from BALC/c to BALB/c mouse grafts as controls. Five allogeneic and 3 syngeneic recipients were humanely killed at predetermined postoperative days 2–12 as well as 14 and 21. Histology was evaluated using hematoxylin-eosin (H&E) staining. We studied the expression of specific markers, including E-cadherin, an epithelial marker; α-smooth muscle actin (SMA), and S100A4, mesenchymal markers, and zinc finger E-box-binding homeobox 1 (ZEB1), an EMT-related transcription factor. Histologic assessment of serial H&E stains of allogeneic grafts showed remarkable pseudostratified respiratory epithelium with subepithelial inflammatory cell infiltration, as well as denuded and flattened epithelium and subepithelial fibrosis. The dynamic epithelial changes occurred earlier than the subepithelial fibrosis. Immunohistochemical evaluation indicated the emergence of α-SMA-positive epithelial cells that were most prominent on day 7. The expression of E-cadherin was attenuated in α-SMA–positive epithelial cells. S100A4 was also expressed in epithelial cells. A few days before the intraepithelial expression of α-SMA, ZEB1 emerged in the nuclei of epithelial cells. We observed expression of an EMT-related transcription factor and mesenchymal markers along with the attenuation of epithelial marker expression in epithelial cells, several days before prominent subepithelial fibrosis formation, results that suggest epithelial cells to play an important fibrosis role in airway remodeling during epithelial to mesenchymal transition.
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影响因子：
8.9
作者：
Gilpin, Sarah E.;Lung, Kalvin C.;Waddell, Thomas K.
通讯作者：
Waddell, Thomas K.
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作者：
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影响因子：
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作者：
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作者：
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