archives@tulane.edu / The kidney develops from the intermediate mesoderm from E10 to P4 in mice and weeks 5 to 34 in humans. The development relies on the physical and signaling interactions between the nephron progenitor cells (NPCs), the stroma progenitor cells, and the ureteric branching tip cells (UBTCs). Kidney development relies on signals that vary based on location and temporally with NPC recruitment order determining the part of the nephron they will form. Kidney organogenesis and nephrogenesis relies on signals from BMPs, growth factors, Wnt, cytokines, and autonomous and exogenous cell proliferation and survival signals. These signals lead into or are regulated by cell metabolism, environmental signals, and chromatin modifications. IUGR is an environmental condition known to cause hypertension, chronic kidney disease, and kidney failure. We hypothesized that disruption of metabolic homeostasis in the nephron progenitor cells in the IUGR fetus impairs nephrogenesis and is the direct link between the maternal environment and nephron endowment leading to adult hypertension and chronic kidney disease (CDK). IUGR from low protein diet caused small pups, small kidneys, increased kidney/body weight ratio. The changes begin at E13.5 with a 30% decrease in ureteric tip count, disorganized/smaller cap mesenchyme (CM) (37.5% decrease in Six2+ NPCs), and smaller kidneys. P0 NPCs show dysregulation to growth factors, Wnt, cell metabolism, and autonomous and exogenous cell proliferation and survival signals shown by bulk RNA-seq and immunofluorescence. Changes from LPD IUGR persist with delayed postnatal growth of skin, hair, body, and kidneys. P21 and adult IUGR show damage to kidneys and increased risk of developing hypertension, and CDK. IUGR LPD is the first hit in the multi-hit disease causation of CDK. The P0 NPCs had dysregulated metabolism and chromatin; postnatal development continues to be dysregulated despite removal of LPD environment. The LPD IUGR model produces a new tool for the study of multi-hit kidney disease. / 1 / Francesca Edgington-Giordano
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_122031 |
| Date | January 2020 |
| Contributors | Edgington-Giordano, Francesca (author), Saifudeen, Zubaida (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 204 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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