Published in
Wiley Open Access, FASEB Journal, S1(27), 2013
DOI: 10.1096/fasebj.27.1_supplement.912.2
Cell Press, Cell Reports, 3(1), p. 241-250, 2012
DOI: 10.1016/j.celrep.2012.01.006
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- ORCID
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- [www.ncbi.nlm.nih.gov] | PDF
- [hal.archives-ouvertes.fr]
- [www.researchgate.net] | PDF
- [www.researchgate.net] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
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Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K2P channels
,
Reza Sharif-Naeini,
Joost H. A. Folgering,
Folgering Jh,
Malika Arhatte,
Martine Jodar,
Charbel El Boustany,
Charbel El Boustany,
Claire Gallian,
Michel Tauc ,
Christophe Duranton,
Isabelle Rubera ,
Florian Lesage,
York Pei,
Peters Dj
and other authors.
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Abstract
How renal epithelial cells respond to increased pressure and the link with kidney disease states remain poorly understood. Pkd1 knockout or expression of a PC2 pathogenic mutant, mimicking the autosomal dominant polycystic kidney disease, dramatically enhances mechanical stress-induced tubular apoptotic cell death. We show the presence of a stretch-activated K(+) channel dependent on the TREK-2 K(2P) subunit in proximal convoluted tubule epithelial cells. Our findings further demonstrate that polycystins protect renal epithelial cells against apoptosis in response to mechanical stress, and this function is mediated through the opening of stretch-activated K(2P) channels. Thus, to our knowledge, we establish for the first time, both in vitro and in vivo, a functional relationship between mechanotransduction and mechanoprotection. We propose that this mechanism is at play in other important pathologies associated with apoptosis and in which pressure or flow stimulation is altered, including heart failure or atherosclerosis.