Browsing by Author "Zweier, Jay L."

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    Bacterial Pyocyanin Inducible KRT6A Accelerates Closure of Epithelial Defect Under Conditions of Mitochondrial Dysfunction
    (Elsevier, 2023) Ghatak, Subhadip; Hemann, Craig; Boslett, James; Singh, Kanhaiya; Sharma, Anu; El Masry, Mohamed S.; Abouhashem, Ahmed Safwat; Ghosh, Nandini; Mathew-Steiner, Shomita S.; Roy, Sashwati; Zweier, Jay L.; Sen, Chandan K.; Surgery, School of Medicine
    Repair of epithelial defect is complicated by infection and related metabolites. Pyocyanin is one such metabolite which is secreted during Pseudomonas aeruginosa infection. Keratinocyte migration is required for the closure of skin epithelial defects. The current work sought to understand pyocyanin-keratinocyte interaction and its significance in tissue repair. SILAC proteomics identified mitochondrial dysfunction as the top pathway responsive to pyocyanin exposure in human keratinocytes. Consistently, functional studies demonstrated mitochondrial stress, depletion of reducing equivalents, and ATP. Strikingly, despite all the above, pyocyanin markedly accelerated keratinocyte migration. Investigation of underlying mechanisms revealed a new function of KRT6A in keratinocytes. KRT6A was pyocyanin inducible and accelerated closure of epithelial defect. Acceleration of closure was associated with poor quality healing including compromised expression of apical junction proteins. This work recognizes KRT6A for its role of enhancing keratinocyte migration under conditions of threat posed by pyocyanin. Qualitatively deficient junctional proteins under conditions of defensive acceleration of keratinocyte migration explains why an infected wound close with deficient skin barrier function as previously reported.