Sunday, March 16, 2025
3/16/2025
PROJECT SUMMARY/ABSTRACT: Kidney disease is a major contributor of death in the U.S. Chronic inflammation is common among individuals with chronic kidney disease. A diet high in salt or low in potassium is associated with increased inflammation and kidney injury. The renal handling of salt and potassium within distal segments of the nephron is linked to the circadian clock. Recently, distal segment cells have been linked to initiating tubulointerstitial inflammation. The research goal is to determine the mechanistic links between BMAL1 and activation of the immune system within distal segment cells of the kidney. Preliminary data identifies BMAL1 as a driver of inflammation in the kidney in response to a low K+/high salt diet, leading to kidney injury. Studies will use novel conditional knockout mouse models to reduce expression and re-express BMAL1 specifically in distal segment cells. The first aim will test the hypothesis that mice with decreased BMAL1 expression within distal segments display lower immune mediated kidney damage in response to low potassium with high salt diet. The second aim will test the hypothesis that BMAL1 within distal segments stimulates pro-inflammatory cytokine production in mice fed a low K+/high salt diet. To test these hypotheses, experiments to determine the localization and extent of renal injury, cytokine/chemokine production, immune cell recruitment and activation in response to a low K+/high salt diet are planned. These studies will establish a novel line of investigation aimed at understanding the link between the clock gene BMAL1 and activation of the immune system in the kidney. The long term goal of this work is to The training plan was carefully designed to build upon career development skills of the project leader focused around research advancement, education, and service to the scientific community. The experiments and career development will take place at the University of Florida, a top ten public research university that provides an outstanding environment for conducting biomedical research. Together, data from this award will provide a foundation for identifying new targets to treat renal inflammation/injury in order to improve the quality of life in individuals with kidney disease. The mentored training plan will provide the project leader with necessary technical and professional skills training needed to become an independent investigator.
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