Novel role for tumor suppressor gene, liver kinase B1, in epithelial–mesenchymal transition leading to chronic lung allograft dysfunction

• DOI: 10.1111/ajt.16903
• Publication Date: 2021-12-03T09:01:38Z
• Authors: Mohammad Rahman; Ranjithkumar Ravi...; Sandhya Bansal; Kristina Sanborn; Sara Bowen; Jennifer Eschbacher; Angara Sureshbabu; Timothy Fleming; Ankit Bharat; Rajat Walia; Ramsey Hachem; Ross M. Bremner; Michael A. Smith; Thalachallour Moh...
• Keywords: Exosome

Epithelial–mesenchymal transition (EMT) has been implicated to play a role in chronic lung allograft dysfunction (CLAD). Liver kinase B1 (LKB1), tumor suppressor gene, can regulate EMT. However, its CLAD development following transplantation remains unknown. Using qRT-PCR, biopsies from transplant recipients with bronchiolitis obliterans syndrome (BOS) demonstrated significant downregulation of LKB1 (p = .0001), compared stable biopsies. To determine the EMT development, we analyzed human bronchial epithelial cell line BEAS-2B. Knockdown by siRNA significantly dysregulated mesenchymal markers expression BEAS-2B cells. Following incubation primary or cells exosomes isolated BOS recipients, was inhibited when incubated BOS-exosome. Incubation BOS-exosomes also decreased and induced air–liquid interface culture method. Our results provide novel evidence that released transplanted lungs undergoing rejection are associated inactivated gene this loss induces leading pathogenesis transplantation.