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Sexual dimorphIsM in renal PrOgenitors to explain gender Specificity In kidney...
Sexual dimorphIsM in renal PrOgenitors to explain gender Specificity In kidney physiOlogy aNd diseases Kidney disorders represent a major global health burden with a significant sexual dimorphism that is largely unexplained. My group first identified the stem cells of the kidney (renal progenitors) and demonstrated their crucial ro... Kidney disorders represent a major global health burden with a significant sexual dimorphism that is largely unexplained. My group first identified the stem cells of the kidney (renal progenitors) and demonstrated their crucial role in kidney disease. Here, I propose that sex hormones regulate number and function of renal progenitors to empower females to face the hemodynamic and metabolic challenges of pregnancy. I further propose that this process impacts on sexual dimorphisms in incidence and outcome of kidney diseases including kidney cancer. A multitude of unpublished data obtained with primary human progenitor cultures and unique mouse models of progenitor-specific sex hormones receptor knockout already support my concepts. I will demonstrate that, starting from the age of fertility, estrogen signaling in renal progenitors supports their survival and self-renewal, which is needed to increase their capacity to generate new podocytes and tubular epithelial cells. I will show that failure to produce a sufficient number of podocytes from estrogen-activated renal progenitors promotes preeclampsia and fetal growth retardation. This is a completely new pathophysiological concept of why women with a mismatch of nephron number and pregnancy-related hyperfiltration develop preeclampsia. I will further demonstrate that the same mechanism protects fertile women from severe forms of glomerular injury unrelated to pregnancy. Finally, I will prove that to compensate for the lower number of renal progenitors, testosterone pushes them to proliferate more in males and that this can explain the increased incidence of most prevalent forms of kidney cancer, that derive from renal progenitors. This topic is a direct continuation of my previous studies on renal progenitors supported by ERC Starting and Consolidator grants and will unravel fundamental paradigms in kidney physiology, adaptation, and disease with important implications for prevention and management of kidney disease. ver más
31/07/2026
UNIFI
2M€
Duración del proyecto: 60 meses Fecha Inicio: 2021-07-05
Fecha Fin: 2026-07-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-07-05
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2020-ADG: ERC ADVANCED GRANT
Cerrada hace 4 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
UNIVERSITA DEGLI STUDI DI FIRENZE No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5