TY  - JOUR
A1  - Henique, Carole
A1  - Bollée, Guillaume
A1  - Loyer, Xavier
A1  - Grahammer, Florian
A1  - Dhaun, Neeraj
A1  - Camus, Marine
A1  - Vernerey, Julien
A1  - Guyonnet, Léa
A1  - Gaillard, François
A1  - Lazareth, Hélène
A1  - Meyer, Charlotte
A1  - Bensaada, Imane
A1  - Legrès, Luc
A1  - Satoh, Takashi
A1  - Akira, Shizuo
A1  - Bruneval, Patrick
A1  - Dimmeler, Stefanie
A1  - Tedgui, Alain
A1  - Karras, Alexandre
A1  - Thervet, Eric
A1  - Nochy, Dominique
A1  - Huber, Tobias
A1  - Mesnard, Laurent
A1  - Lenoir, Olivia
A1  - Tharaux, Pierre-Louis
T1  - Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis
T2  - Nature Communications
N2  - 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.
KW  - Glomerular diseases
KW  - Mechanisms of disease
KW  - Molecular medicine
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46798
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-467987
SN  - 2041-1723
N1  - Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 8
IS  - 1, Art. 1829
SP  - 1
EP  - 15
PB  - Nature Publishing Group UK
CY  - [London]
ER  -