2011
DOI: 10.1016/j.jtcvs.2010.10.006
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Immunosuppression-induced bronchial epithelial–mesenchymal transition: A potential contributor to obliterative bronchiolitis

Abstract: Overall, we found that certain immunosuppressive agents may contribute to partial epithelial-mesenchymal transition in bronchial epithelial cells, specifically increasing production of excessive extracellular matrix proteins. This may provide novel insights into the pathogenesis of obliterative bronchiolitis after lung transplant.

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Cited by 16 publications
(12 citation statements)
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“…In addition, the activation of signaling pathways involved in EMT, in particular TGF-b or Wnt pathways, was also reported in the lungs of patients affected by pulmonary fibrosis (36,40,41). Moreover, rat bronchial epithelial cells (RL-65) treated with sirolimus displayed mesenchymal traits (42). Therefore, our results suggest the intriguing idea that the inhibitory action of rapalogs on mTORC1 may promote the EMT of bronchoalveaolar cells, thereby contributing to the ILD pathophysiologic process.…”
Section: Discussionsupporting
confidence: 67%
“…In addition, the activation of signaling pathways involved in EMT, in particular TGF-b or Wnt pathways, was also reported in the lungs of patients affected by pulmonary fibrosis (36,40,41). Moreover, rat bronchial epithelial cells (RL-65) treated with sirolimus displayed mesenchymal traits (42). Therefore, our results suggest the intriguing idea that the inhibitory action of rapalogs on mTORC1 may promote the EMT of bronchoalveaolar cells, thereby contributing to the ILD pathophysiologic process.…”
Section: Discussionsupporting
confidence: 67%
“…To determine the contributing factors for EMT-related bronchiolitis obliterans after lung transplantation, immunosuppressive therapy regimens were evaluated to see if they contributed to the fibroproliferative transformation. Results of the study revealed that treatment with cyclosporine, azathioprine, mycophenolic acid and sirolimus resulted in an increase in TGF-β and morphological changes consistent with transition of epithelial cells to the mesenchymal cell type 3. Similarly, another study showed that immunosuppressive therapy contributes to renal tubular EMT 3.…”
Section: Discussionmentioning
confidence: 94%
“…A unique finding that has not been described in the literature and may be observed in EMB from heart transplant recipients is epithelial to mesenchymal transition (EMT), a reparative process mediated by transforming growth factor beta-1 (TGF-β1), a profibrotic agent. EMTs have been identified in lung and kidney transplant recipients and in lung transplant patients receiving immunosuppressants such as cyclosporine, azathioprine, mycophenolic acid and sirolimus 3. Here, we describe a case of a patient who received a heart allograft and a post-transplantation EMB revealed a hypercellular, atypical lesion that after thorough work-up and evaluation, appears to be consistent with EMT.…”
Section: Introductionmentioning
confidence: 81%
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“…174 Although TGF-β is the main orchestrator of the airway remodeling process after lung transplantation, its effect can be largely modified by an inflammatory environment and cytokines like TNFα or IL-1β. 175,176 Besides, pollutants 177 or immunossupressive drugs 178 have also been described as EMT inducers. Moreover, release of reactive oxygen species by macrophagesorneutrophilsafterlung transplantation 179 associated with a decrease in the counterbalancing factors, such as ascorbic acid, urate, glutathione 57 or Clara Cell Secretory Protein 16, 180 promotes the upregulation of the vascular endothelial growth factor, which may further stimulate fibrosis.…”
Section: Consequences On the Lung Allograftmentioning
confidence: 99%