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Implication de l'urothélium intrarénal dans les mécanismes précoses de régénération au cours de néphropathies obstructive et ischémique expérimentales

Abstract : Conversely to the bladder urothelium, intrarenal urothelium phenotype and function have not raised much interest. The main focus of this study is to characterize murine intrarenal urothelium in physiological condition, following unilateral ureteral obstruction and ischemia/reperfusion models with or without acute renal failure. Our results suggest that intrarenal urothelium is different from the bladder urothelium and play a potential key role in renal regeneration. This urothelium structure extends deeply in renal parenchyma up to the fornices located near the corticomedullary junction in the vicinity of lobar vessels. Possessing the characteristics of epithelial progenitor cells, intrarenal urothelium has a remarkable plasticity allowing an adaptative response to hypoxia and hyperpressure: it changes its phenotype into 'bladder-like' urothelium thus ensuring an effective barrier. In renal unilateral ischemia, urothelial cells constitute the first cell contingent to proliferate and precede tubular regeneration. Proliferating urothelial cells do not migrate and do not home into injured tubules. In both models intrarenal urothelial cell proliferation is FGF7/FGFR2IIIb-mediated. Establishing the kinetics of urothelial and renal tubular cell proliferation after ischemia we observed that following ischemic acute renal failure, cell proliferation is inhibited through FGF7 down regulation and can be prevented by recombinant FGF7 administration. Thus, FGF7 could be a potential treatment of acute renal failure acting both as a preconditioning factor to prevent renal injury and also accelerating renal repair through tubular regeneration
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Submitted on : Monday, June 3, 2013 - 2:43:56 PM
Last modification on : Sunday, June 26, 2022 - 9:39:30 AM
Long-term archiving on: : Wednesday, September 4, 2013 - 4:13:36 AM

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  • HAL Id : tel-00829555, version 1

Citation

Alexis Girshovich. Implication de l'urothélium intrarénal dans les mécanismes précoses de régénération au cours de néphropathies obstructive et ischémique expérimentales. Physiologie [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66396⟩. ⟨tel-00829555⟩

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