Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

Anie Azroyan; Virna Cortez-Retamozo; Richard Bouley; Rachel Liberman; Ye Chun Ruan; Evgeny Kiselev; Kenneth A Jacobson; Mikael J Pittet; Dennis Brown; Sylvie Breton

doi:10.1371/journal.pone.0121419

Back

Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

Journal article

Open access

Peer reviewed

Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

Anie Azroyan, Virna Cortez-Retamozo, Richard Bouley, Rachel Liberman, Ye Chun Ruan, Evgeny Kiselev, Kenneth A Jacobson, Mikael J Pittet, Dennis Brown and Sylvie Breton

PloS one, Vol.10(3), pp.e0121419-e0121419

2015

DOI: https://doi.org/10.1371/journal.pone.0121419

PMCID: PMC4370445

PMID: 25799465

Abstract

Inflammation - pathology

Cells, Cultured

Receptors, Purinergic P2Y - metabolism

Kidney Tubules, Collecting - pathology

Male

Inflammation - immunology

Kidney Tubules, Collecting - cytology

Kidney Tubules, Collecting - metabolism

Inflammation - metabolism

Animals

MAP Kinase Signaling System - drug effects

Uridine Diphosphate Glucose - pharmacology

Dogs

Madin Darby Canine Kidney Cells

Mice

Neutrophils - metabolism

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.

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0121419View

Published (Version of record) Open

Metrics

36 Record Views

See more details

Details

Title: Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor
Creators: Anie Azroyan - 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
Virna Cortez-Retamozo - Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America
Richard Bouley - 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
Rachel Liberman - 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
Ye Chun Ruan - 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
Evgeny Kiselev - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Kenneth A Jacobson - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Mikael J Pittet - Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America
Dennis Brown - 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
Sylvie Breton - 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
Publication Details: PloS one, Vol.10(3), pp.e0121419-e0121419
Publisher: United States
Grant note: DK097124 / NIDDK NIH HHS R56 DK042956 / NIDDK NIH HHS HD040793 / NICHD NIH HHS DK43351 / NIDDK NIH HHS ZIA DK031116-28 / Intramural NIH HHS R01 DK097124 / NIDDK NIH HHS DK57521 / NIDDK NIH HHS R37 DK042956 / NIDDK NIH HHS P30 DK057521 / NIDDK NIH HHS R01 HD040793 / NICHD NIH HHS P30 DK043351 / NIDDK NIH HHS DK042956 / NIDDK NIH HHS R01 DK042956 / NIDDK NIH HHS
Identifiers: 9923987666401921
Copyright: © 2015 Azroyan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Academic Unit: Department of Biology
Language: English
Resource Type: Journal article

Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

Abstract

UN Sustainable Development Goals (SDGs)

Files and links (1)

Metrics

Details

Brandeis University Social media