PMID- 28434946
OWN - NLM
STAT- MEDLINE
DCOM- 20180306
LR  - 20220321
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 19
DP  - 2017 May
TI  - Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related 
      Injury.
PG  - 73-83
LID - S2352-3964(17)30155-X [pii]
LID - 10.1016/j.ebiom.2017.04.011 [doi]
AB  - Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and 
      fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted 
      by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 
      (MCP-1) has been shown to attract macrophages in kidney diseases. P2X7 receptors 
      (P2X7R) are highly expressed on macrophages and are essential components of 
      pro-inflammatory signaling in multiple tissues. Here we show that in diabetic 
      patients, renal P2X7R expression is associated with severe mesangial expansion, 
      impaired glomerular filtration (</=40ml/min/1.73sq.m.), and increased interstitial 
      fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells 
      cultured under high glucose conditions. In mice, P2X7R-deficiency prevented 
      glomerular macrophage attraction and collagen IV deposition; however, the more 
      severe interstitial inflammation and fibrosis often seen in human diabetic kidney 
      diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor 
      (AZ11657312) can reduce renal macrophage accrual following the establishment of 
      hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest 
      that P2X7R activation may contribute to the high prevalence of kidney disease 
      found in diabetics.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Menzies, Robert I
AU  - Menzies RI
AD  - British Heart Foundation Centre for Cardiovascular Science, The University of 
      Edinburgh, Edinburgh, UK. Electronic address: robert.menzies@ed.ac.uk.
FAU - Booth, John W R
AU  - Booth JWR
AD  - UCL Centre for Nephrology, University College London, London, UK.
FAU - Mullins, John J
AU  - Mullins JJ
AD  - British Heart Foundation Centre for Cardiovascular Science, The University of 
      Edinburgh, Edinburgh, UK.
FAU - Bailey, Matthew A
AU  - Bailey MA
AD  - British Heart Foundation Centre for Cardiovascular Science, The University of 
      Edinburgh, Edinburgh, UK.
FAU - Tam, Frederick W K
AU  - Tam FWK
AD  - Imperial College Renal and Transplant Centre, Department of Medicine, Imperial 
      College London, London, UK.
FAU - Norman, Jill T
AU  - Norman JT
AD  - UCL Centre for Nephrology, University College London, London, UK.
FAU - Unwin, Robert J
AU  - Unwin RJ
AD  - UCL Centre for Nephrology, University College London, London, UK; Cardiovascular 
      and Metabolic Diseases (CVMD) iMed, AstraZeneca, Gothenburg, Sweden.
LA  - eng
GR  - FS/15/60/31510/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
DEP - 20170420
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Purinergic P2X Receptor Antagonists)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 0 (Tetrazoles)
RN  - 4P5DXU1F8Q (3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/analogs & derivatives/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Diabetes Mellitus, Experimental/*metabolism
MH  - Diabetes Mellitus, Type 1/*metabolism
MH  - Diabetic Nephropathies/*metabolism/pathology
MH  - Humans
MH  - Hyperglycemia/*metabolism
MH  - Kidney/*metabolism/pathology
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Mesangial Cells/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Purinergic P2X Receptor Antagonists/pharmacology
MH  - Pyridines/pharmacology
MH  - Rats, Wistar
MH  - Receptors, Purinergic P2X7/genetics/*metabolism
MH  - Tetrazoles/pharmacology
PMC - PMC5440600
OTO - NOTNLM
OT  - CKD
OT  - Cytokine
OT  - Glucose
OT  - P2
OT  - Purine
OT  - Renal
EDAT- 2017/04/25 06:00
MHDA- 2018/03/07 06:00
PMCR- 2017/04/20
CRDT- 2017/04/25 06:00
PHST- 2017/02/26 00:00 [received]
PHST- 2017/03/31 00:00 [revised]
PHST- 2017/04/06 00:00 [accepted]
PHST- 2017/04/25 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2017/04/25 06:00 [entrez]
PHST- 2017/04/20 00:00 [pmc-release]
AID - S2352-3964(17)30155-X [pii]
AID - 10.1016/j.ebiom.2017.04.011 [doi]
PST - ppublish
SO  - EBioMedicine. 2017 May;19:73-83. doi: 10.1016/j.ebiom.2017.04.011. Epub 2017 Apr 
      20.