Details

Autor(en) / Beteiligte

• Henique, Carole
• Bollée, Guillaume
• Loyer, Xavier
• Grahammer, Florian
• Dhaun, Neeraj
• Camus, Marine
• Vernerey, Julien
• Guyonnet, Léa
• Gaillard, François
• Lazareth, Hélène
• Meyer, Charlotte
• Bensaada, Imane
• Legrès, Luc
• Satoh, Takashi
• Akira, Shizuo
• Bruneval, Patrick
• Dimmeler, Stefanie
• Tedgui, Alain
• Karras, Alexandre
• Thervet, Eric
• Nochy, Dominique
• Huber, Tobias B
• Mesnard, Laurent
• Lenoir, Olivia
• Tharaux, Pierre-Louis

Titel

Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis

Ist Teil von

• Nature communications, 2017-11, Vol.8 (1), p.1829-15, Article 1829

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 p57 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 p57 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.