Chronic lung allograft rejection, known as obliterative bronchiolitis (OB), is the leading cause of death in lung transplant patients. Although OB pathogenesis is not fully understood, in this issue of the JCI, Jiang and colleagues report that tissue hypoxia resulting in dysfunctional airway microvasculature precedes the airway fibrosis characteristic of OB. In addition, a relative deficiency of allograft endothelial cell–derived HIF-1α contributes to this process. Data showing that overexpressing HIF-1α restores the microvascular airway normoxia and prevents airway fibrosis highlight a novel role for vascular biology in OB pathogenesis.
David S. Wilkes
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Bronchial anastomotic complications as a microvascular disruption in a mouse model of airway transplantation
Khan MA, Bhusal S, Lau CL, Krupnick AS |
Frontiers in Immunology | 2025 |
Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts
S Kazmi, M Khan, T Shamma, A Altuhami, H Ahmed, A Assiri, D Broering |
International journal of molecular sciences | 2022 |
IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts
MA Khan, GA Ashoor, T Shamma, F Alanazi, A Altuhami, S Kazmi, HA Ahmed, AM Assiri, DC Broering |
Cells | 2021 |
Airway hypoxia in lung transplantation
S Pasupneti, MR Nicolls |
Current Opinion in Physiology | 2019 |
The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
H Xu, A Abuduwufuer, W Lv, Z Zhou, Y Yang, C Zhang, J Hu |
Journal of Cardiothoracic Surgery | 2019 |
Regulation of Endothelial-to-Mesenchymal Transition by MicroRNAs in Chronic Allograft Dysfunction:
EK Glover, N Jordan, NS Sheerin, S Ali |
Transplantation | 2019 |
Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation
BD Kraft, HB Suliman, EC Colman, K Mahmood, MG Hartwig, CA Piantadosi, SL Shofer |
American journal of respiratory and critical care medicine | 2016 |
HIF-1α Regulates CD55 in Airway Epithelium
PH Pandya, AJ Fisher, EA Mickler, CJ Temm, KP Lipking, A Gracon, K Rothhaar, GE Sandusky, M Murray, K Pollok, J Renbarger, J Blum, T Lahm, DS Wilkes |
American journal of respiratory cell and molecular biology | 2016 |
Targeting Hypoxia-Inducible Factor 1 to Stimulate Tissue Vascularization:
GL Semenza |
Journal of Investigative Medicine | 2015 |
The endothelial ADMA/NO pathway in hypoxia-related chronic respiratory diseases
N Lüneburg, L Harbaum, JK Hennigs |
BioMed Research International | 2014 |
Hypoxia-Inducible Factors in Physiology and Medicine
GL Semenza |
Cell | 2012 |
Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success
X Lin, W Li, J Lai, M Okazaki, S Sugimoto, S Yamamoto, X Wang, AE Gelman, D Kreisel, AS Krupnick |
Journal of Thoracic Disease | 2012 |
IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis
R Vittal, L Fan, DS Greenspan, EA Mickler, B Gopalakrishnan, H Gu, HL Benson, C Zhang, W Burlingham, OW Cummings, DS Wilkes |
American journal of physiology. Lung cellular and molecular physiology | 2012 |
Hypoxia and hypoxia mimetics inhibit TNF-dependent VCAM1 induction in the 5A32 endothelial cell line via a hypoxia inducible factor dependent mechanism
TV Cartee, KJ White, M Newton-West, RA Swerlick |
Journal of Dermatological Science | 2011 |