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

Hélène Lazareth 1, 2 Carole Henique 1, 3 Olivia Lenoir 1 Victor Puelles 4, 5, 6 Martin Flamant 7 Guillaume Bollée 1 Cécile Fligny 1 Marine Camus 1 Léa Guyonnet 8 Corinne Millien 1 François Gaillard 1 Anna Chipont 1 Blaise Robin 1 Sylvie Fabrega 9, 10 Neeraj Dhaun 11 Eric Camerer 1 Oliver Kretz 5, 12 Florian Grahammer 12, 5 Fabian Braun 5, 12 Tobias Huber 5, 12 Dominique Nochy 13 Chantal Mandet 13 Patrick Bruneval 13 Laurent Mesnard 14 Eric Thervet 15, 1 Alexandre Karras 16, 1 François Le Naour 17 Eric Rubinstein 18 Claude Boucheix 18 Antigoni Alexandrou 2 Marcus Moeller 4 Cedric Bouzigues 2 Pierre-Louis Tharaux 1, 15, *
* Corresponding author
1 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
2 LOB - Laboratoire d'Optique et Biosciences
3 IMRB - Institut Mondor de Recherche Biomédicale
4 Department of Nephrology and Clinical Immunology [Aachen, Germany]
5 Faculty of Medicine - Department of Medicine III [Hamburg, Germany]
6 Department of Nephrology and Center for Inflammatory Diseases [Melbourne, VIC, Australia]
7 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
8 LIH - Luxembourg Institute of Health
9 IRNEM - IFR Necker-Enfants Malades
10 Plate-forme Necker - La Fondation Imagine – Institut des maladies génétiques
11 Department of Renal Medicine [Scotland, UK]
12 Renal Division [Freiburg, Germany]
13 Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou]
14 Service de néphrologie et de transplantation rénale [CHU Tenon]
15 Service de Néphrologie et Hémodialyse [CHU HEGP]
16 HEGP - Hôpital Européen Georges Pompidou [APHP]
17 Physiopathologie et traitement des maladies du foie
18 Modèles de Cellules Souches Malignes et Thérapeutiques
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.
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Submitted on : Tuesday, January 14, 2020 - 2:36:22 PM
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Hélène Lazareth, Carole Henique, Olivia Lenoir, Victor Puelles, Martin Flamant, et al.. The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression. Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.3303. ⟨10.1038/s41467-019-11013-2⟩. ⟨inserm-02439082⟩

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