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

Abstract

BackgroundMany 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.MethodsWe 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.ResultsInflammatory 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).ConclusionsIn 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.

Loading Imatinib inside targeted nanoparticles to prevent Bronchiolitis Obliterans Syndrome

“…3 ). This is relevant since epithelial damage is one of the most crucial insults to epithelial mesenchymal transition (EMT) 18 , the precursor step of tracheal fibroobliteration 19 . In the same context, the cytokine TGF-β has been found to have pleiotropic immunoregulatory properties: it plays a central role in EMT induction, it is a critical mediator of extracellular remodeling and fibroproliferation and it is involved in the pathogenesis of a wide variety of disease states.…”

Epithelial to mesenchymal transition in endomyocardial biopsies from orthotopic heart transplant recipients

“…However, it has been a cause of airway remodelling after lung transplant and deterioration of kidney transplants. It has been noted that post-lung transplant, many patients develop bronchiolitis obliterans, and based on immunobiology chemistry, a reduction in epithelial markers and an increase in mesenchymal markers: vimentin and α-SMA were identified indicating a transition from epithelium to mesenchymal cell type 8 14. In kidney transplantation, biopsies from deteriorating allograft kidneys with impaired functions showed a reduction in epithelial markers and an increase in mesenchymal markers 15…”

Organ preservation with targeted rapamycin nanoparticles: a pre-treatment strategy preventing chronic rejection in vivo

“…There is growing appreciation that factors occurring early in the life of the graft may affect late outcomes. Expanding evidence suggests that blunting the immunologic activation of donor antigen presenting cells, such as endothelial and epithelial cells, prior to or after transplantation may be the key to downregulating early inflammatory processes which leads to downstream graft loss 22–24. To that end, we have devised a novel nanoparticle that, via a targeting moiety, facilitates nanoparticle uptake in endothelial and epithelial cells in vitro and in vivo .…”

“…Expanding evidence suggests that blunting the immunologic activation of donor antigen presenting cells, such as endothelial and epithelial cells, prior to or after transplantation may be the key to downregulating early inflammatory processes which leads to downstream graft loss. 22 – 24 To that end, we have devised a novel nanoparticle that, via a targeting moiety, facilitates nanoparticle uptake in endothelial and epithelial cells in vitro and in vivo . Using these unique characteristics we are able to deliver therapeutic payloads ex vivo and “pre-treat” organs prior to the onslaught of ischemia/reperfusion injury.…”