Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

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

doi:10.1371/journal.pone.0121419

Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

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

Research output: Journal article publication › Journal article › Academic research › peer-review

72 Citations (Scopus)

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 P2Y 14 (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.

Original language	English
Article number	e0121419
Journal	PLoS ONE
Volume	10
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0121419
Publication status	Published - 23 Mar 2015
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

More information

10.1371/journal.pone.0121419

Cite this

@article{e37cc695ce9f4ec2903cbe802fec4aad,

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 P2Y 14 (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.",

author = "Anie Azroyan and Virna Cortez-Retamozo and Richard Bouley and Rachel Liberman and Yechun Ruan and Evgeny Kiselev and Jacobson, {Kenneth A.} and Pittet, {Mikael J.} and Dennis Brown and Sylvie Breton",

year = "2015",

month = mar,

day = "23",

doi = "10.1371/journal.pone.0121419",

language = "English",

volume = "10",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "3",

}

TY - JOUR

T1 - Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

AU - Azroyan, Anie

AU - Cortez-Retamozo, Virna

AU - Bouley, Richard

AU - Liberman, Rachel

AU - Ruan, Yechun

AU - Kiselev, Evgeny

AU - Jacobson, Kenneth A.

AU - Pittet, Mikael J.

AU - Brown, Dennis

AU - Breton, Sylvie

PY - 2015/3/23

Y1 - 2015/3/23

N2 - 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 P2Y 14 (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.

AB - 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 P2Y 14 (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.

UR - http://www.scopus.com/inward/record.url?scp=84925740494&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0121419

DO - 10.1371/journal.pone.0121419

M3 - Journal article

C2 - 25799465

SN - 1932-6203

VL - 10

JO - PLoS ONE

JF - PLoS ONE

IS - 3

M1 - e0121419

ER -

Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor

Abstract

ASJC Scopus subject areas

More information

Other files and links

Fingerprint

Cite this