The pleural mesothelium and transforming growth factor-β1 pathways in restrictive allograft syndrome: A pre-clinical investigation

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Annelore SacreasStijn E Verleden

Abstract

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-β1 (TGF-β1) in restrictive allograft syndrome (RAS). TGF-β1 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. TGF-β1 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 α-smooth muscle actin (p = 0.0089) mRNA expression and protein levels in isolated pleural tissue. Moreover, TGF-...Continue Reading

Citations

Mar 7, 2020·Expert Review of Molecular Diagnostics·Osnat Shtraichman, Joshua M Diamond
Aug 31, 2019·The European Respiratory Journal·Antoine Roux, Stijn E Verleden
Nov 26, 2020·Cells·Janne Kaes Group The Leuven Lung Transplant
May 15, 2021·The European Respiratory Journal·Olivier Brugiere, Stijn E Verleden
Dec 12, 2020·The European Respiratory Journal·Carmela MorroneAli Önder Yildirim
May 17, 2021·Transplantation Reviews·Eline A van der PloegC Tji Gan
Dec 30, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Saskia Bos, Andrew J Fisher

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