Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K(2P) channels.

File Description SizeFormat 
Cell Reports_1_3_2012.pdfPublished version2.28 MBAdobe PDFView/Open
Title: Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K(2P) channels.
Authors: Peyronnet, R
Sharif-Naeini, R
Folgering, JH
Arhatte, M
Jodar, M
El Boustany, C
Gallian, C
Tauc, M
Duranton, C
Rubera, I
Lesage, F
Pei, Y
Peters, DJ
Somlo, S
Sachs, F
Patel, A
Honoré, E
Duprat, F
Item Type: Journal Article
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.
Issue Date: 29-Mar-2012
URI: http://hdl.handle.net/10044/1/18956
DOI: http://dx.doi.org/10.1016/j.celrep.2012.01.006
Start Page: 241
End Page: 250
Journal / Book Title: Cell Rep
Volume: 1
Issue: 3
Copyright Statement: Copyright © 2012 The Authors. Licenced under a Creative Commons CC BY-NC-ND licence
Conference Place: United States
Appears in Collections:National Heart and Lung Institute



This item is licensed under a Creative Commons License Creative Commons