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
N1 - Funding Information:
This work was supported by Institut National de Santé et de la Recherche Medicalé (INSERM), research grants from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ ERC grant agreement n°107037), European Research Projects on Rare Diseases E-Rare-2 JTC 2011 from l’Agence Nationale de la Recherche (ANR) of France and the Freiburg Institute for Advanced Studies to P.-L.T. We thank National Health and Medical Research Council of Australia, the Humboldt Foundation and German Society of Nephrology for supporting VGP. We are grateful to Assistance Publique des Hôpitaux de Paris for supporting H.L. We thank the European Research Council for supporting C.H. and O.L. We thank Nano-K for supporting the Laboratoire d’Op-tique et de Biosciences at Ecole Polytechnique. We also thank Elizabeth Huc, Nicolas Perez, and the ERI970 team for assistance in animal care and handling, Nicolas Sorhaindo for biochemical measurements (ICB-IFR2, Laboratoire de Biochimie, Hôpital Bichat, Paris, France), Alain Schmitt and Jean-Marc Masse for transmission electron microscopy (Institut Cochin, Paris, France), Corinne Lesaffre for histological stainings, and technical support by Valerie Oberüber and Anja Obser. We acknowledge excellent administrative support from Véronique Oberweis, Annette De Rueda, Martine Autran, Bruno Pillard and Philippe Coudol. Dr P-L Tharaux was supported by the Freiburg Institute for Advanced Studies (FRIAS).
Publisher Copyright:
© 2019, The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85069628803&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/31341160
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 -