title: An RNA interference screen identifies new avenues for nephroprotection.
abstract: Acute kidney injury is a major public health problem, which is commonly caused by renal ischemia and is associated with a high risk of mortality and long-term disability. Efforts to develop a treatment for this condition have met with very limited success. We used an RNA interference screen to identify genes (BCL2L14, BLOC1S2, C2ORF42, CPT1A, FBP1, GCNT3, RHOB, SCIN, TACR1, and TNFAIP6) whose suppression improves survival of kidney epithelial cells in in vitro models of oxygen and glucose deprivation. Some of the genes also modulate the toxicity of cisplatin, an anticancer agent whose use is currently limited by nephrotoxicity. Furthermore, pharmacological inhibition of TACR1 product NK1R was protective in a model of mouse renal ischemia, attesting to the in vivo relevance of our findings. These data shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Zynda
authors.affiliation: Department of Cardiovascular and Metabolic Discovery, F. Hoffmann-La Roche Ltd, Bau 70/307, Basel CH4070, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Schott
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: M
authors.initials: M
authors.lastname: Babagana
authors.affiliation: Department of Cardiovascular and Metabolic Discovery, F. Hoffmann-La Roche Ltd, Bau 70/307, Basel CH4070, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Gruener
authors.affiliation: Department of Cardiovascular and Metabolic Discovery, F. Hoffmann-La Roche Ltd, Bau 70/307, Basel CH4070, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Wernher
authors.affiliation: Department of Pharmaceutical Sciences, Translational Technologies and Bioinformatics, F. Hoffmann-La Roche Ltd, Bau 70/307, Basel CH4070, Switzerland.
authors.forename: G D
authors.initials: GD
authors.lastname: Nguyen
authors.affiliation: Department of Pharmaceutical Sciences, Translational Technologies and Bioinformatics, F. Hoffmann-La Roche Ltd, Bau 70/307, Basel CH4070, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Ebeling
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Kandel
mesh_terms: D000818:Animals; D002460:Cell Line; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D034622:RNA Interference