Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor.
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 intercal...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4370445?pdf=render |
id |
doaj-e26b6902856e46068197796a4c3de6c7 |
---|---|
record_format |
Article |
spelling |
doaj-e26b6902856e46068197796a4c3de6c72020-11-24T21:35:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012141910.1371/journal.pone.0121419Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor.Anie AzroyanVirna Cortez-RetamozoRichard BouleyRachel LibermanYe Chun RuanEvgeny KiselevKenneth A JacobsonMikael J PittetDennis BrownSylvie BretonUncontrolled 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.http://europepmc.org/articles/PMC4370445?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anie Azroyan Virna Cortez-Retamozo Richard Bouley Rachel Liberman Ye Chun Ruan Evgeny Kiselev Kenneth A Jacobson Mikael J Pittet Dennis Brown Sylvie Breton |
spellingShingle |
Anie Azroyan Virna Cortez-Retamozo Richard Bouley Rachel Liberman Ye Chun Ruan Evgeny Kiselev Kenneth A Jacobson Mikael J Pittet Dennis Brown Sylvie Breton Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. PLoS ONE |
author_facet |
Anie Azroyan Virna Cortez-Retamozo Richard Bouley Rachel Liberman Ye Chun Ruan Evgeny Kiselev Kenneth A Jacobson Mikael J Pittet Dennis Brown Sylvie Breton |
author_sort |
Anie Azroyan |
title |
Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. |
title_short |
Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. |
title_full |
Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. |
title_fullStr |
Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. |
title_full_unstemmed |
Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor. |
title_sort |
renal intercalated cells sense and mediate inflammation via the p2y14 receptor. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4370445?pdf=render |
work_keys_str_mv |
AT anieazroyan renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT virnacortezretamozo renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT richardbouley renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT rachelliberman renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT yechunruan renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT evgenykiselev renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT kennethajacobson renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT mikaeljpittet renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT dennisbrown renalintercalatedcellssenseandmediateinflammationviathep2y14receptor AT sylviebreton renalintercalatedcellssenseandmediateinflammationviathep2y14receptor |
_version_ |
1725944428696174592 |