ROLE OF TRPV4 MECHANOSENSING REGULATING MACROPHAGE FUNCTIONS IN INFLAMMATORY DISEASES

dc.contributor.advisorRahaman, Shaik Oen_US
dc.contributor.authorDutta, Bidishaen_US
dc.contributor.departmentNutritionen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2025-02-07T06:38:36Z
dc.date.issued2024en_US
dc.description.abstractMacrophages are the most versatile cells of the hematopoietic system with roles in homeostasis, host-tissue development, innate immune response and tissue repair. Although the inflammatory activation and maintenance signals are tightly regulated, an imbalance in them results in unchecked inflammation resulting in cellular and tissue damage. Macrophages can affect most if not all phases of inflammation owing to their ability to adopt distinct functional states, secrete cytokines and phagocytose pathogens and debris. Recent evidence suggests that beyond biochemical cues, mechanical forces, like changing matrix stiffness in the tissue microenvironment, can shape immune cell functions involved in inflammation. These cells convert mechanical stimuli to biochemical signals in a process called mechanotransduction, regulating a multitude of cellular functions. However, knowledge about the molecular mediators of mechanotransduction and their functions in macrophage phenotypic and functional change is largely missing, highlighting the need for studying mechanosensory molecules such as ion channels. The present study focuses on the role of a specific mechanosensitive ion channel, Transient Receptor Potential Vanilloid 4 (TRPV4), in the regulation of macrophage mediated inflammatory responses. Given its emerging role in inflammatory diseases like fibrosis, arthritis, foreign body response (FBR), TRPV4’s contribution to macrophage behavior in inflammation is of growing interest. Employing cellular imaging and molecular biology techniques such as Ca2+ influx assays, immunohistochemistry, immunoblotting, and single nuclei RNA sequencing we delineate mechanisms by which biomechanical stimuli-mediated activation of TRPV4 affects macrophage function. We elucidate TRPV4’s role in macrophage mechanotransduction, providing a mechanistic understanding of inflammatory disease pathophysiology which could lead to the development of potential therapeutics for disease intervention.en_US
dc.identifierhttps://doi.org/10.13016/y8sm-lfxx
dc.identifier.urihttp://hdl.handle.net/1903/33775
dc.language.isoenen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pqcontrolledBiomechanicsen_US
dc.subject.pqcontrolledMolecular biologyen_US
dc.titleROLE OF TRPV4 MECHANOSENSING REGULATING MACROPHAGE FUNCTIONS IN INFLAMMATORY DISEASESen_US
dc.typeDissertationen_US

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