title: Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor.
abstract: Uncontrolled inflammation is one of the leading causes of kidney failure. Pro-inflammatory responses can occur in the absence of infection, a process called sterile inflammation. Here we show that the purinergic receptor P2Y14 (GPR105) is specifically and highly expressed in collecting duct intercalated cells (ICs) and mediates sterile inflammation in the kidney. P2Y14 is activated by UDP-glucose, a damage-associated molecular pattern molecule (DAMP) released by injured cells. We found that UDP-glucose increases pro-inflammatory chemokine expression in ICs as well as MDCK-C11 cells, and UDP-glucose activates the MEK1/2-ERK1/2 pathway in MDCK-C11 cells. These effects were prevented following inhibition of P2Y14 with the small molecule PPTN. Tail vein injection of mice with UDP-glucose induced the recruitment of neutrophils to the renal medulla. This study identifies ICs as novel sensors, mediators and effectors of inflammation in the kidney via P2Y14.
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Anie
authors: A
authors: Azroyan
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Virna
authors: V
authors: Cortez-Retamozo
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Richard
authors: R
authors: Bouley
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Rachel
authors: R
authors: Liberman
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Ye Chun
authors: YC
authors: Ruan
authors: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Evgeny
authors: E
authors: Kiselev
authors: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Kenneth A
authors: KA
authors: Jacobson
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Mikael J
authors: MJ
authors: Pittet
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Dennis
authors: D
authors: Brown
authors: Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Sylvie
authors: S
authors: Breton
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology*; D018048:Receptors, Purinergic P2
chemical_list: D058470:Receptors, Purinergic P2Y; D014532:Uridine Diphosphate Glucose; C518528:P2Y14 receptor, human; D018048:Receptors, Purinergic P2