The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

Hélène Lazareth, Carole Henique*, Olivia Lenoir, Victor G. Puelles, Martin Flamant, Guillaume Bollée, Cécile Fligny, Marine Camus, Lea Guyonnet, Corinne Millien, François Gaillard, Anna Chipont, Blaise Robin, Sylvie Fabrega, Neeraj Dhaun, Eric Camerer, Oliver Kretz, Florian Grahammer, Fabian Braun, Tobias B. HuberDominique Nochy, Chantal Mandet, Patrick Bruneval, Laurent Mesnard, Eric Thervet, Alexandre Karras, François Le Naour, Eric Rubinstein, Claude Boucheix, Antigoni Alexandrou, Marcus J. Moeller, Cédric Bouzigues, Pierre Louis Tharaux

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here we show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions.

Original languageEnglish
Article number3303
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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