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. Huber; Dominique 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

doi:10.1038/s41467-019-11013-2

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. Huber

Dominique 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

Institut National de la Santé et de la Recherche Médicale (Inserm)
INSERM U869
Paris Centre de Recherche Cardiovasculaire (PARCC)
Renal Division
Pôle de Biologie
Université Paris-Saclay
Institut Mondor de Recherche Biomédicale
Université de PARIS XII
Department of Nephrology and Clinical Immunology
University Hospital RWTH Aachen
Department of Medicine III
University Medical Center Hamburg-Eppendorf
Department of Nephrology and Center for Inflammatory Diseases
Monash University
Medical and Infectious Diseases ICU (MI2)
National Cytometry Platform
Luxembourg Institute of Health
Laboratoire de Probabilités et Modèles Aléatoires
Department of Renal Medicine
Royal Infirmary of Edinburgh
Renal Division
University Clinic Freiburg
Department of Pathology
Groupe Hospitalier Lariboisiere-Fernand Widal Assistance Publique-Hopitaux de Paris (AP-HP)
Critical Care Nephrology and Kidney Transplantation
Paris-Saclay University
University Paris-Saclay

Research output: Contribution to journal › Article › peer-review

76 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 language	English
Article number	3303
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11013-2
Publication status	Published - 1 Dec 2019
Externally published	Yes

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10.1038/s41467-019-11013-2

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Lazareth, H., Henique, C., Lenoir, O., Puelles, V. G., Flamant, M., Bollée, G., Fligny, C., Camus, M., Guyonnet, L., Millien, C., Gaillard, F., Chipont, A., Robin, B., Fabrega, S., Dhaun, N., Camerer, E., Kretz, O., Grahammer, F., Braun, F., ... Tharaux, P. L. (2019). The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression. Nature Communications , 10(1), Article 3303. https://doi.org/10.1038/s41467-019-11013-2

@article{db2191392ab44cce8f3252f99d63fb7c,

title = "The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression",

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.",

author = "H{\'e}l{\`e}ne Lazareth and Carole Henique and Olivia Lenoir and Puelles, \{Victor G.\} and Martin Flamant and Guillaume Boll{\'e}e and C{\'e}cile Fligny and Marine Camus and Lea Guyonnet and Corinne Millien and Fran{\c c}ois Gaillard and Anna Chipont and Blaise Robin and Sylvie Fabrega and Neeraj Dhaun and Eric Camerer and Oliver Kretz and Florian Grahammer and Fabian Braun and Huber, \{Tobias B.\} and Dominique Nochy and Chantal Mandet and Patrick Bruneval and Laurent Mesnard and Eric Thervet and Alexandre Karras and \{Le Naour\}, Fran{\c c}ois and Eric Rubinstein and Claude Boucheix and Antigoni Alexandrou and Moeller, \{Marcus J.\} and C{\'e}dric Bouzigues and Tharaux, \{Pierre Louis\}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-11013-2",

language = "English",

volume = "10",

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Lazareth, H, Henique, C, Lenoir, O, Puelles, VG, Flamant, M, Bollée, G, Fligny, C, Camus, M, Guyonnet, L, Millien, C, Gaillard, F, Chipont, A, Robin, B, Fabrega, S, Dhaun, N, Camerer, E, Kretz, O, Grahammer, F, Braun, F, Huber, TB, Nochy, D, Mandet, C, Bruneval, P, Mesnard, L, Thervet, E, Karras, A, Le Naour, F, Rubinstein, E, Boucheix, C, Alexandrou, A, Moeller, MJ, Bouzigues, C & Tharaux, PL 2019, 'The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression', Nature Communications , vol. 10, no. 1, 3303. https://doi.org/10.1038/s41467-019-11013-2

TY - JOUR

T1 - The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

AU - Lazareth, Hélène

AU - Henique, Carole

AU - Lenoir, Olivia

AU - Puelles, Victor G.

AU - Flamant, Martin

AU - Bollée, Guillaume

AU - Fligny, Cécile

AU - Camus, Marine

AU - Guyonnet, Lea

AU - Millien, Corinne

AU - Gaillard, François

AU - Chipont, Anna

AU - Robin, Blaise

AU - Fabrega, Sylvie

AU - Dhaun, Neeraj

AU - Camerer, Eric

AU - Kretz, Oliver

AU - Grahammer, Florian

AU - Braun, Fabian

AU - Huber, Tobias B.

AU - Nochy, Dominique

AU - Mandet, Chantal

AU - Bruneval, Patrick

AU - Mesnard, Laurent

AU - Thervet, Eric

AU - Karras, Alexandre

AU - Le Naour, François

AU - Rubinstein, Eric

AU - Boucheix, Claude

AU - Alexandrou, Antigoni

AU - Moeller, Marcus J.

AU - Bouzigues, Cédric

AU - Tharaux, Pierre Louis

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-11013-2

DO - 10.1038/s41467-019-11013-2

M3 - Article

C2 - 31341160

AN - SCOPUS:85069628803

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3303

ER -

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

Abstract

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