Developmental Renal Glomerular Defects at the Origin of Glomerulocystic Disease

Arianna Fiorentino, Armelle Christophorou, Filippo Massa, Serge Garbay, Magali Chiral, Mette Ramsing, Maria Rasmussen, Marie-Claire Gubler, Bettina Bessieres, Laurence Heidet, Evelyne Fischer, Marco Pontoglio

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Abstrakt

The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glomerular arterioles) and the urinary pole (the tubular outflow). We demonstrate that this remodeling is genetically programmed. In fact, in mouse and human, the absence of HNF1B impairs the remodeling/separation of the two poles, leading to trapping and constriction of the tubular outflow inside the glomerulus. This aberration gives rise to obstructive glomerular dilations upon the initiation of primary urine production. In this context, we show that pharmacological decrease of glomerular filtration significantly contains cystic expansion. From a developmental point of view, our study discloses a crucial event on glomerular patterning affecting the "inside-outside" fate of the epithelia in the renal glomerulus.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind33
Udgave nummer4
Sider (fra-til)108304
ISSN2211-1247
DOI
StatusUdgivet - 27. okt. 2020

Bibliografisk note

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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