Physiology Seminar, Co- hosted by Cystic Fibrosis Translational Research Centre: Dr. Albert van der Vliet, "The NADPH Oxidase DUOX1 in Redox-Dependent Epithelial Homeostasis, Extracellular Matrix Remodeling, and Fibrotic lung disease"

Friday, December 1, 2023 11:00to12:00
McIntyre Medical Building Room 1034, 3655 promenade Sir William Osler, Montreal, QC, H3G 1Y6, CA

NADPH oxidases (NOX) represent a family of dedicated oxidant-generating enzymes that serve widespread biological roles, ranging from host defense, cell proliferation or differentiation, to immune regulation. In the lung, the NOX isoform DUOX1 is expressed primarily within the respiratory epithelium, and our past studies have demonstrated its role in innate epithelial responses to various injurious triggers (including pathogens and asthma-inducing allergens), by mediating various wound responses via cellular redox signaling pathways involving tyrosine kinases such as SRC and EGFR. Among these DUOX1-mediated injury responses is the epithelial secretion of the alarmin IL-33, which serves to maintain epithelial integrity by activating type 2 immune responses. We also demonstrated that epithelial DUOX1 expression and activation is enhanced during allergic asthma, and contributes to type 2 inflammation and airway remodeling as major features of allergic airways disease. More recently, we also uncovered an apparent functional role for DUOX1 in macrophages, indicating its contributing roles in macrophage recruitment and profibrotic activation in models of allergic airway inflammation or pulmonary fibrosis. Lastly, based on previous studies linking DUOX1 to extracellular oxidative crosslinking processes in various organisms via activation of secreted heme peroxidases, we are currently exploring a link between DUOX1 and peroxidasin (PXDN), a recently identified heme peroxidase involved in collagen IV crosslinking within basement membranes (BM), and have obtained preliminary evidence for a concerted role of DUOX1 and PXDN in oxidative matrix remodeling that may promote lung stiffening in fibrotic lung disease. Curiously, these PXDN-mediated cross-linking mechanisms rely on the presence of bromide (Br-), and also give rise to alternative oxidative ECM modifications, including the formation of 3-bromo-tyrosine (Br-Y) in several BM proteins. The relevance and therapeutic implications of these various oxidative mechanisms for fibrotic lung disease will be discussed.


This seminar will take place in-person and online ( details in attached poster below) All are welcome!

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