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The pleural mesothelium and TGF-β1 pathways in restrictive allograft syndrome : a pre-clinical investigation

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Abstract
BACKGROUND: Chronic lung allograft dysfunction (CLAD) hampers long-term survival after lung transplantation. Common fibrosis-related mechanisms in idiopathic pulmonary fibrosis and CLAD instigated the consideration of investigating the differential regulation of pleural mesothelium and transforming growth factor-beta(1) (TGF-beta(1)) in restrictive allograft syndrome (RAS). METHODS: TGF-beta(1) was assessed in bronchoalveolar lavage (BAL) fluid using enzyme-linked immunoassay and via immune staining of explant biopsies. To assess the role of the pleura, explanted bronchiolitis obliterans syndrome (BOS) and RAS lungs were compared using computed tomography scans, calretinin stainings, Western blot, and quantititative real-time PCR. Last, a pleural mesothelial cell line was used to assess mesothelial-to-mesenchymal transition and its inhibition. RESULTS: TGF-beta(1) was increased in BAL of RAS patients (p = 0.035), and was present in the (sub) pleural area of biopsies. Explanted RAS lungs demonstrated an increased volume fraction of pleura (p = 0.0004), a higher proportion of calretinin-positive stainings (p = 0.0032), and decreased E-cadherin (p = 0.019) and increased alpha-smooth muscle actin (p = 0.0089) mRNA expression and protein levels in isolated pleural tissue. Moreover, TGF-beta(1) stimulation of pleural mesothelial cells led to a phenotypical switch to mesenchymal cells, accompanied with an increased migratory capacity. Interleukin-1 alpha was able to accentuate TGF-beta(1). induced mesothelial-to-mesenchymal transition. None of the tested drugs could inhibit mesothelial-to-mesenchymal transition at the used concentrations. CONCLUSIONS: Our results support an interplay between TGF-beta(1) and the pleural mesothelium in the pathophysiology of RAS. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.
Keywords
BRONCHIOLITIS OBLITERANS SYNDROME, FACTOR-BETA, EPITHELIAL-CELLS, TGF-BETA, LUNG, DYSFUNCTION, PATHOPHYSIOLOGY, MYOFIBROBLASTS, PHENOTYPES, FIBROSIS, Lung transplantation, chronic lung allograft dysfunction, restrictive allograft syndrome, TGF-B, fibrosis, pleura, mesothelium to mesenchymal transition

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MLA
Sacreas, Annelore, et al. “The Pleural Mesothelium and TGF-Β1 Pathways in Restrictive Allograft Syndrome : A Pre-Clinical Investigation.” JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol. 38, no. 5, 2019, pp. 570–79.
APA
Sacreas, A., H. von der Thüsen, J., P. P. van den Bosch, T., Weynand, B., K. Verbeken, E., Debbaut, C., … E. Verleden, S. (2019). The pleural mesothelium and TGF-β1 pathways in restrictive allograft syndrome : a pre-clinical investigation. JOURNAL OF HEART AND LUNG TRANSPLANTATION, 38(5), 570–579.
Chicago author-date
Sacreas, Annelore, Jan H. von der Thüsen, Thierry P. P. van den Bosch, Birgit Weynand, Erik K. Verbeken, Charlotte Debbaut, Dirk E. Van Raemdonck, Robin Vos, and Stijn E. Verleden. 2019. “The Pleural Mesothelium and TGF-Β1 Pathways in Restrictive Allograft Syndrome : A Pre-Clinical Investigation.” JOURNAL OF HEART AND LUNG TRANSPLANTATION 38 (5): 570–79.
Chicago author-date (all authors)
Sacreas, Annelore, Jan H. von der Thüsen, Thierry P. P. van den Bosch, Birgit Weynand, Erik K. Verbeken, Charlotte Debbaut, Dirk E. Van Raemdonck, Robin Vos, and Stijn E. Verleden. 2019. “The Pleural Mesothelium and TGF-Β1 Pathways in Restrictive Allograft Syndrome : A Pre-Clinical Investigation.” JOURNAL OF HEART AND LUNG TRANSPLANTATION 38 (5): 570–579.
Vancouver
1.
Sacreas A, H. von der Thüsen J, P. P. van den Bosch T, Weynand B, K. Verbeken E, Debbaut C, et al. The pleural mesothelium and TGF-β1 pathways in restrictive allograft syndrome : a pre-clinical investigation. JOURNAL OF HEART AND LUNG TRANSPLANTATION. 2019;38(5):570–9.
IEEE
[1]
A. Sacreas et al., “The pleural mesothelium and TGF-β1 pathways in restrictive allograft syndrome : a pre-clinical investigation,” JOURNAL OF HEART AND LUNG TRANSPLANTATION, vol. 38, no. 5, pp. 570–579, 2019.
@article{8598871,
  abstract     = {BACKGROUND: Chronic lung allograft dysfunction (CLAD) hampers long-term survival after lung transplantation. Common fibrosis-related mechanisms in idiopathic pulmonary fibrosis and CLAD instigated the consideration of investigating the differential regulation of pleural mesothelium and transforming growth factor-beta(1) (TGF-beta(1)) in restrictive allograft syndrome (RAS).

METHODS: TGF-beta(1) was assessed in bronchoalveolar lavage (BAL) fluid using enzyme-linked immunoassay and via immune staining of explant biopsies. To assess the role of the pleura, explanted bronchiolitis obliterans syndrome (BOS) and RAS lungs were compared using computed tomography scans, calretinin stainings, Western blot, and quantititative real-time PCR. Last, a pleural mesothelial cell line was used to assess mesothelial-to-mesenchymal transition and its inhibition.

RESULTS: TGF-beta(1) was increased in BAL of RAS patients (p = 0.035), and was present in the (sub) pleural area of biopsies. Explanted RAS lungs demonstrated an increased volume fraction of pleura (p = 0.0004), a higher proportion of calretinin-positive stainings (p = 0.0032), and decreased E-cadherin (p = 0.019) and increased alpha-smooth muscle actin (p = 0.0089) mRNA expression and protein levels in isolated pleural tissue. Moreover, TGF-beta(1) stimulation of pleural mesothelial cells led to a phenotypical switch to mesenchymal cells, accompanied with an increased migratory capacity. Interleukin-1 alpha was able to accentuate TGF-beta(1). induced mesothelial-to-mesenchymal transition. None of the tested drugs could inhibit mesothelial-to-mesenchymal transition at the used concentrations.

CONCLUSIONS: Our results support an interplay between TGF-beta(1) and the pleural mesothelium in the pathophysiology of RAS. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.},
  author       = {Sacreas, Annelore and H. von der Thüsen, Jan and P. P. van den Bosch, Thierry and Weynand, Birgit and K. Verbeken, Erik and Debbaut, Charlotte and E. Van Raemdonck, Dirk and Vos, Robin and E. Verleden, Stijn},
  issn         = {1053-2498},
  journal      = {JOURNAL OF HEART AND LUNG TRANSPLANTATION},
  keywords     = {BRONCHIOLITIS OBLITERANS SYNDROME,FACTOR-BETA,EPITHELIAL-CELLS,TGF-BETA,LUNG,DYSFUNCTION,PATHOPHYSIOLOGY,MYOFIBROBLASTS,PHENOTYPES,FIBROSIS,Lung transplantation,chronic lung allograft dysfunction,restrictive allograft syndrome,TGF-B,fibrosis,pleura,mesothelium to mesenchymal transition},
  language     = {eng},
  number       = {5},
  pages        = {570--579},
  title        = {The pleural mesothelium and TGF-β1 pathways in restrictive allograft syndrome : a pre-clinical investigation},
  url          = {http://dx.doi.org/10.1016/j.healun.2019.02.001},
  volume       = {38},
  year         = {2019},
}

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