The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans

Abstract Background Many patients who receive lung transplantation (LT) operations develop varying degrees of bronchiolitis obliterans (BO) after the surgeries. Epithelial-mesenchymal transition (EMT) is considered to be related to the process of bronchiolitis obliterans. In this study we simulated...

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Main Authors: Chong Zhang, Yuequn Niu, Li Yu, Wang Lv, Haichao Xu, Abudumailamu Abuduwufuer, Jinlin Cao, Jian Hu
Format: Article
Language:English
Published: BMC 2017-12-01
Series:Journal of Cardiothoracic Surgery
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13019-017-0673-6
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author Chong Zhang
Yuequn Niu
Li Yu
Wang Lv
Haichao Xu
Abudumailamu Abuduwufuer
Jinlin Cao
Jian Hu
author_facet Chong Zhang
Yuequn Niu
Li Yu
Wang Lv
Haichao Xu
Abudumailamu Abuduwufuer
Jinlin Cao
Jian Hu
author_sort Chong Zhang
collection DOAJ
description Abstract Background Many patients who receive lung transplantation (LT) operations develop varying degrees of bronchiolitis obliterans (BO) after the surgeries. Epithelial-mesenchymal transition (EMT) is considered to be related to the process of bronchiolitis obliterans. In this study we simulated the pathological process of post-lung transplantation bronchiolitis obliterans, and explored the correlation between BO and EMT of small airway epithelial cells. Methods We transplanted the left lungs of F344 rats to Lewis rats by the Tri-cuff anastomosis and established the allogeneic rat left lung orthotopic transplantation model. Cyclosporine and lipopolysaccharide were administrated appropriately after the surgery. The histological structure and the expression levels of the EMT markers was observed with the methods of HE staining, Masson staining and immunohistochemistry. The analysis of enumeration data was performed using Fisher’s Exact test and Spearman’s rank correlation was used for the correlation analysis. Results Inflammatory cell infiltration, fibroplasia of bronchiole walls and significant lumen stenosis were found in the pulmonary mesenchyme of the transplanted lungs. The positive expression rate of E-cadherin in the transplanted lungs was 38.50% (5/13), significantly lower than that in the normal lung tissues [87.50% (7/8)] (P < 0.05), while the positive expression rate of Vimentin was 76.92% (10/13) which is significantly higher than that in the normal lung tissues [25.00% (2/8)] (P < 0.05). And a negative correlation existed between the expression levels of E-cadherin and Vimentin (r = −0.750, P < 0.01). Conclusions In the disease model we established in this study, we found pathological changes that met BO characteristics happened in the transplanted lungs. Meanwhile, the small airway epithelial cells of transplanted lungs underwent an epithelial-mesenchymal transition, which indicated a role of EMT in the BO airway remodeling.
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spelling doaj.art-0c2dd1225bad4bba8be598e7232d3ae22022-12-21T18:25:07ZengBMCJournal of Cardiothoracic Surgery1749-80902017-12-011211610.1186/s13019-017-0673-6The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliteransChong Zhang0Yuequn Niu1Li Yu2Wang Lv3Haichao Xu4Abudumailamu Abuduwufuer5Jinlin Cao6Jian Hu7Department of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityDepartment of Thoracic Surgery, First Affiliated Hospital of Zhejiang UniversityAbstract Background Many patients who receive lung transplantation (LT) operations develop varying degrees of bronchiolitis obliterans (BO) after the surgeries. Epithelial-mesenchymal transition (EMT) is considered to be related to the process of bronchiolitis obliterans. In this study we simulated the pathological process of post-lung transplantation bronchiolitis obliterans, and explored the correlation between BO and EMT of small airway epithelial cells. Methods We transplanted the left lungs of F344 rats to Lewis rats by the Tri-cuff anastomosis and established the allogeneic rat left lung orthotopic transplantation model. Cyclosporine and lipopolysaccharide were administrated appropriately after the surgery. The histological structure and the expression levels of the EMT markers was observed with the methods of HE staining, Masson staining and immunohistochemistry. The analysis of enumeration data was performed using Fisher’s Exact test and Spearman’s rank correlation was used for the correlation analysis. Results Inflammatory cell infiltration, fibroplasia of bronchiole walls and significant lumen stenosis were found in the pulmonary mesenchyme of the transplanted lungs. The positive expression rate of E-cadherin in the transplanted lungs was 38.50% (5/13), significantly lower than that in the normal lung tissues [87.50% (7/8)] (P < 0.05), while the positive expression rate of Vimentin was 76.92% (10/13) which is significantly higher than that in the normal lung tissues [25.00% (2/8)] (P < 0.05). And a negative correlation existed between the expression levels of E-cadherin and Vimentin (r = −0.750, P < 0.01). Conclusions In the disease model we established in this study, we found pathological changes that met BO characteristics happened in the transplanted lungs. Meanwhile, the small airway epithelial cells of transplanted lungs underwent an epithelial-mesenchymal transition, which indicated a role of EMT in the BO airway remodeling.http://link.springer.com/article/10.1186/s13019-017-0673-6Lung transplantationChronic rejectionBronchiolitis obliteransEpithelial-mesenchymal transitionE-cadherinVimentin
spellingShingle Chong Zhang
Yuequn Niu
Li Yu
Wang Lv
Haichao Xu
Abudumailamu Abuduwufuer
Jinlin Cao
Jian Hu
The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans
Journal of Cardiothoracic Surgery
Lung transplantation
Chronic rejection
Bronchiolitis obliterans
Epithelial-mesenchymal transition
E-cadherin
Vimentin
title The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans
title_full The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans
title_fullStr The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans
title_full_unstemmed The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans
title_short The role of epithelial-mesenchymal transition in the post-lung transplantation bronchiolitis obliterans
title_sort role of epithelial mesenchymal transition in the post lung transplantation bronchiolitis obliterans
topic Lung transplantation
Chronic rejection
Bronchiolitis obliterans
Epithelial-mesenchymal transition
E-cadherin
Vimentin
url http://link.springer.com/article/10.1186/s13019-017-0673-6
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