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

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  • Hélène Lazareth

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970
    Assistance Publique-Hôpitaux de Paris, Université de Paris
    Ecole polytechnique, CNRS UMR7645, INSERM U1182, Université Paris-Saclay)

  • Carole Henique

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970
    Inserm U955, Equipe 21, Université Paris Est Créteil)

  • Olivia Lenoir

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Victor G. Puelles

    (University Hospital RWTH Aachen
    University Medical Center Hamburg-Eppendorf
    Monash University)

  • Martin Flamant

    (Xavier Bichat University Hospital, Université de Paris)

  • Guillaume Bollée

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Cécile Fligny

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Marine Camus

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Lea Guyonnet

    (Luxembourg Institute of Health)

  • Corinne Millien

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • François Gaillard

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Anna Chipont

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Blaise Robin

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Sylvie Fabrega

    (Université de Paris, Institut Imagine, Plateforme Vecteurs Viraux et Transfert de Gènes, IFR94, Hôpital Necker Enfants-Malades)

  • Neeraj Dhaun

    (Royal Infirmary of Edinburgh)

  • Eric Camerer

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970)

  • Oliver Kretz

    (University Medical Center Hamburg-Eppendorf
    University of Freiburg)

  • Florian Grahammer

    (University Medical Center Hamburg-Eppendorf
    University of Freiburg)

  • Fabian Braun

    (University Medical Center Hamburg-Eppendorf
    University of Freiburg)

  • Tobias B. Huber

    (University Medical Center Hamburg-Eppendorf
    University of Freiburg)

  • Dominique Nochy

    (Assistance Publique-Hôpitaux de Paris)

  • Chantal Mandet

    (Assistance Publique-Hôpitaux de Paris)

  • Patrick Bruneval

    (Assistance Publique-Hôpitaux de Paris)

  • Laurent Mesnard

    (Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche S1155, Pierre and Marie Curie University)

  • Eric Thervet

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970
    Assistance Publique-Hôpitaux de Paris, Université de Paris)

  • Alexandre Karras

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970
    Assistance Publique-Hôpitaux de Paris, Université de Paris)

  • François Naour

    (Inserm U1193, Université Paris-Sud)

  • Eric Rubinstein

    (Inserm U935, Université Paris-Sud)

  • Claude Boucheix

    (Inserm U935, Université Paris-Sud)

  • Antigoni Alexandrou

    (Ecole polytechnique, CNRS UMR7645, INSERM U1182, Université Paris-Saclay)

  • Marcus J. Moeller

    (University Hospital RWTH Aachen)

  • Cédric Bouzigues

    (Ecole polytechnique, CNRS UMR7645, INSERM U1182, Université Paris-Saclay)

  • Pierre-Louis Tharaux

    (Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
    Université de Paris, UMR-S970
    Assistance Publique-Hôpitaux de Paris, Université de Paris)

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.

Suggested Citation

  • Hélène Lazareth & Carole Henique & Olivia Lenoir & Victor G. Puelles & Martin Flamant & Guillaume Bollée & Cécile Fligny & Marine Camus & Lea Guyonnet & Corinne Millien & François Gaillard & Anna Chip, 2019. "The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11013-2
    DOI: 10.1038/s41467-019-11013-2
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    Cited by:

    1. Larissa Seifert & Gunther Zahner & Catherine Meyer-Schwesinger & Naemi Hickstein & Silke Dehde & Sonia Wulf & Sarah M. S. Köllner & Renke Lucas & Dominik Kylies & Sarah Froembling & Stephanie Zielinsk, 2023. "The classical pathway triggers pathogenic complement activation in membranous nephropathy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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