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Journal articles
Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis
Carole Henique
1, 2
Guillaume Bollée
1, 3
Xavier Loyer
1
Florian Grahammer
4, 5, 6
Neeraj Dhaun
1, 7
Marine Camus
1
Julien Vernerey
1
Léa Guyonnet
1
François Gaillard
1
Hélène Lazareth
1
Charlotte Meyer
6
Imane Bensaada
1
Luc Legrès
8
Takashi Satoh
9
Shizuo Akira
9
Patrick Bruneval
10, 11
Stefanie Dimmeler
12
Alain Tedgui
1
Alexandre Karras
1, 11, 13
Eric Thervet
13, 1, 11
Dominique Nochy
10, 11
Tobias Huber
4, 5, 6
Laurent Mesnard
14
Olivia Lenoir
1, *
Pierre-Louis Tharaux
1, 13, *
*
Corresponding author
Carole Henique 1, 2
Author
Guillaume Bollée 1, 3
Author
Xavier Loyer 1
Author
Florian F. Grahammer 4, 5, 6
Mail :
Author
François Gaillard 1
Author
Hélène Lazareth 1
Author
Charlotte Meyer 6
Author
Imane Bensaada 1
Author
Luc Legrès 8
Mail :
Author
Takashi Satoh 9
Author
Shizuo Akira 9
Author
Patrick Bruneval 10, 11
Author
Stefanie Dimmeler 12
Author
Alain Tedgui 1
Author
Alexandre Karras 1, 11, 13
Author
Eric Thervet 13, 1, 11
Author
Dominique Nochy 10, 11
Author
Tobias Huber 4, 5, 6
Author
Laurent Mesnard 14
Author
Olivia Lenoir 1
Mail :
Correspondent author
Pierre-Louis Tharaux 1, 13
Mail :
Correspondent author
1
PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire (56 rue Leblanc
75015 PARIS
FRANCE - France)
- HEGP - Hôpital Européen Georges Pompidou [APHP] : U970 (20, rue Leblanc, 75015 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR_S 970 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U970 (101, rue de Tolbiac, 75013 Paris - France)
2
IMRB - Institut Mondor de Recherche Biomédicale (8 rue du Général Sarrail 94010 Créteil - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U955 (101, rue de Tolbiac, 75013 Paris - France)
- IFR10 (France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 : UMR955 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
3
CRCHUM - Centre de recherche du Chum [Montréal] (Université de Montréal, Québec, Canada - Canada)
- CHUM - Centre Hospitalier de l'Université de Montréal (Montréal - Canada)
4
Faculty of Medicine - Department of Medicine III [Hamburg, Germany] (Germany)
- UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (Martinistraße 52 20251 Hamburg - Germany)
5
Faculty of Medicine - Department of Medicine IV [Freiburg, Germany] (Germany)
- University of Freiburg [Freiburg] (Friedrichstr. 39 79098 Freiburg - Germany)
6
BIOSS - Centre for Biological Signaling Studies [Freiburg] (Schänzlestr. 18
79104 Freiburg - Germany)
- University of Freiburg [Freiburg] (Friedrichstr. 39 79098 Freiburg - Germany)
7
BHF CoRE - British Heart Foundation Centre of Research Excellence [Edinburgh, UK] (United Kingdom)
8
UMR 1165 - Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (Institut Universitaire Hématologie (IUH), Centre Hayem - Hôpital St Louis - 1 avenue Claude Vellefaux 75475 Paris Cedex 10 - France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1165 (101, rue de Tolbiac, 75013 Paris - France)
9
Laboratory of Host Defense / WPI Immunology Frontier Research Centre [Osaka, Japan] (Japan)
- Osaka University [Osaka] (3-3-138 Sugimoto Sumiyoshi-ku, Osaka 558-8585 - Japan)
10
Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou] (20 Rue Leblanc, 75015 Paris. - France)
- HEGP - Hôpital Européen Georges Pompidou [APHP] (20, rue Leblanc, 75015 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
11
Paris Descartes - Département Hospitalo-Universitaire Paris Ouest (France)
- UPD5 - Université Paris Descartes - Paris 5 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
12
Centre for Molecular Medicine - Institute of Cardiovascular Regeneration [Frankfurt, Germany] (Germany)
- Goethe-University Frankfurt am Main (Theodor-W.-Adorno-Platz 1 , 60323 Frankfurt am Main - Germany)
13
Service de Néphrologie et Hémodialyse [CHU HEGP] (20 Rue Leblanc, 75015 Paris - France)
- APHP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- HEGP - Hôpital Européen Georges Pompidou [APHP] (20, rue Leblanc, 75015 Paris - France)
14
Remodelage et Reparation du Tissu Renal (Hopital Tenon PARIS VI 4, Rue de La Chine 75970 PARIS CEDEX 20 - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U702 (101, rue de Tolbiac, 75013 Paris - France)
Abstract : Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most aggressive form of acquired glomerular disease. While most therapeutic approaches involve potentially toxic immunosuppressive strategies, the pathophysiology remains incompletely understood. Podocytes are glomerular epithelial cells that are normally growth-arrested because of the expression of cyclin-dependent kinase (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation of their differentiated phenotype and proliferate. Here we demonstrate that microRNA-92a (miR-92a) is enriched in podocytes of patients and mice with RPGN. The CDK inhibitor p57Kip2 is a major target of miR-92a that constitutively safeguards podocyte cell cycle quiescence. Podocyte-specific deletion of miR-92a in mice de-repressed the expression of p57Kip2 and prevented glomerular injury in RPGN. Administration of an anti-miR-92a after disease initiation prevented albuminuria and kidney failure, indicating miR-92a inhibition as a potential therapeutic strategy for RPGN. We demonstrate that miRNA induction in epithelial cells can break glomerular tolerance to immune injury.
Document type :
Journal articles
Complete list of metadatas
https://www.hal.inserm.fr/inserm-02439029
Contributor : Pierre-Louis Tharaux <>
Submitted on : Tuesday, January 14, 2020 - 2:22:03 PM
Last modification on : Thursday, April 9, 2020 - 11:49:12 AM
Document(s) archivé(s) le : Wednesday, April 15, 2020 - 4:31:06 PM
Contributor : Pierre-Louis Tharaux <>
Submitted on : Tuesday, January 14, 2020 - 2:22:03 PM
Last modification on : Thursday, April 9, 2020 - 11:49:12 AM
Document(s) archivé(s) le : Wednesday, April 15, 2020 - 4:31:06 PM
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s41467-017-01885-7.pdf
Publication funded by an institution
Identifiers
- HAL Id : inserm-02439029, version 1
- DOI : 10.1038/s41467-017-01885-7
- PUBMED : 29184126
- PUBMEDCENTRAL : PMC5705755
Collections
IMRB | UPEC-UPEM | UPEC | UPMC | UNIV-PARIS5 | UNIV-PARIS7 | USPC | SORBONNE-UNIVERSITE | UP-SANTE
Citation
Carole Henique, Guillaume Bollée, Xavier Loyer, Florian Grahammer, Neeraj Dhaun, et al.. Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis. Nature Communications, Nature Publishing Group, 2017, 8 (1), pp.1829. ⟨10.1038/s41467-017-01885-7⟩. ⟨inserm-02439029⟩
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