Premium
Mechanoprotection by Polycystins Against Apoptosis is Mediated Through the Opening of Stretch‐Activated K2P Channels
Author(s) -
Duprat Fabrice,
Peyronnet Remi,
SharifNaeini Reza,
Folgering Joost H.A.,
Arhatte Malika,
Jodar Martine,
El Boustany Charbel,
Gallian Claire,
Tauc Michel,
Duranton Christophe,
Rubera Isabelle,
Lesage Florian,
Pei York,
Peters Dorien,
Somlo Stefan,
Sachs Frederick,
Patel Amanda Jane,
Honoré Eric
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.912.2
Subject(s) - pkd1 , autosomal dominant polycystic kidney disease , mechanotransduction , apoptosis , polycystic kidney disease , microbiology and biotechnology , kidney , chemistry , hek 293 cells , biology , gene , endocrinology , biochemistry
How cells sense and adapt to mechanical stress remains poorly understood. The TREK two‐pore K + (K2P) subunits underlie the stretch‐activated K + ‐selective channels (SAKs). Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2 genes, encoding the polycystins PC1 and PC2. Cystogenesis results mainly from an increase in tubular epithelial cells proliferation. Nevertheless, how a few cysts (typically less than 1% of the nephrons) may impair the function of the majority (99%) of non‐cystic nephrons, ultimately leading to kidney failure, is still an unresolved question. An increase in intra‐renal mechanical stress leading to tubular cells apoptosis and formation of atubular nephrons is a proposed mechanism. In our study, Pkd1 knock out or expression of a PC2 pathogenic mutant enhances tubular cells apoptosis induced by mechanical stress. We show that polycystins protect renal epithelial cells against mechanical stress and this effect is mediated through the opening of SAKs. We establish for the first time, both in vitro and in vivo, a functional relationship between mechanotransduction and mechanoprotection (Peyronnet et al. 2012 Cell Rep 1(3): 241–250). Funding: ANR, FRM, EEC, FRHTA, FRC, Human Frontier, Fondation de France, AFM, AIRG, Région PACA, SFHTA.