title: Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K(2P) channels.
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.
authors: Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS 7275, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors: Rémi
authors: R
authors: Peyronnet
authors: Reza
authors: R
authors: Sharif-Naeini
authors: Joost H A
authors: JH
authors: Folgering
authors: Malika
authors: M
authors: Arhatte
authors: Martine
authors: M
authors: Jodar
authors: Charbel
authors: C
authors: El Boustany
authors: Claire
authors: C
authors: Gallian
authors: Michel
authors: M
authors: Tauc
authors: Christophe
authors: C
authors: Duranton
authors: Isabelle
authors: I
authors: Rubera
authors: Florian
authors: F
authors: Lesage
authors: York
authors: Y
authors: Pei
authors: Dorien J M
authors: DJ
authors: Peters
authors: Stefan
authors: S
authors: Somlo
authors: Frederick
authors: F
authors: Sachs
authors: Amanda
authors: A
authors: Patel
authors: Eric
authors: E
authors: Honoré
authors: Fabrice
authors: F
authors: Duprat
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D002522:Chlorocebus aethiops; D019610:Cytoprotection / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D055786:Gene Knockout Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D013314:Stress, Mechanical; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D024683:Potassium Channels, Tandem Pore Domain; D021122:Protein Subunits; D050396:TRPP Cation Channels; D004281:Docosahexaenoic Acids