PMID- 17473221
OWN - NLM
STAT- MEDLINE
DCOM- 20070921
LR  - 20161122
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 56
IP  - 9
DP  - 2007 Sep
TI  - The vascular ectonucleotidase ENTPD1 is a novel renoprotective factor in diabetic 
      nephropathy.
PG  - 2371-9
AB  - Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) (also known as CD39) is 
      the dominant vascular ectonucleotidase. By hydrolyzing ATP and ADP to AMP, ENTPD1 
      regulates ligand availability to a large family of P2 (purinergic) receptors. 
      Modulation of extracellular nucleotide metabolism is an important factor in 
      several acute and subacute models of vascular injury. We hypothesized that 
      aberrant nucleotide signaling would promote chronic glomerular injury in diabetic 
      nephropathy. Inducing diabetes in ENTPD1-null mice with streptozotocin resulted 
      in increased proteinuria and more severe glomerular sclerosis compared with 
      matched diabetic wild-type mice. Diabetic ENTPD1-null mice also had more 
      glomerular fibrin deposition and glomerular plasminogen activator inhibitor-1 
      (PAI-1) staining than wild-type controls. In addition, ENTPD1-null mice showed 
      increased glomerular inflammation, in association with higher levels of monocyte 
      chemoattractant protein-1 (MCP-1) expression. Mesangial cell PAI-1 and MCP-1 mRNA 
      expression were upregulated by ATP and UTP but not ADP or adenosine in vitro. The 
      stable nucleotide analog ATPgammaS stimulated sustained expression of PAI-1 and 
      MCP-1 in vitro, whereas the stable adenosine analog NECA 
      [5'-(N-ethylcarboxamido)adenosine] downregulated expression of both genes. 
      Extracellular nucleotide-stimulated upregulation of MCP-1 is, at least in part, 
      protein kinase C dependent. We conclude that ENTPD1 is a vascular protective 
      factor in diabetic nephropathy that modulates glomerular inflammation and 
      thromboregulation.
FAU - Friedman, David J
AU  - Friedman DJ
AD  - Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, 
      Harvard Medical School, Boston, Massachusetts 02215, USA. 
      dfriedma@caregroup.harvard.edu
FAU - Rennke, Helmut G
AU  - Rennke HG
FAU - Csizmadia, Eva
AU  - Csizmadia E
FAU - Enjyoji, Keiichi
AU  - Enjyoji K
FAU - Robson, Simon C
AU  - Robson SC
LA  - eng
GR  - R01 HL063972-03/HL/NHLBI NIH HHS/United States
GR  - HL57307/HL/NHLBI NIH HHS/United States
GR  - R01 HL063972-06/HL/NHLBI NIH HHS/United States
GR  - HL076540/HL/NHLBI NIH HHS/United States
GR  - R01 HL063972-07/HL/NHLBI NIH HHS/United States
GR  - R01 HL063972-05/HL/NHLBI NIH HHS/United States
GR  - R01 HL063972-08/HL/NHLBI NIH HHS/United States
GR  - R01 HL063972/HL/NHLBI NIH HHS/United States
GR  - HL63972/HL/NHLBI NIH HHS/United States
GR  - R01 HL063972-04/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070501
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Antigens, CD)
RN  - 0 (Serum Albumin)
RN  - 5W494URQ81 (Streptozocin)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 3.6.1.5 (Apyrase)
RN  - EC 3.6.1.5 (CD39 antigen)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*genetics/metabolism
MH  - Apyrase/deficiency/*genetics
MH  - Creatinine/blood
MH  - Diabetes Mellitus, Experimental/*complications/pathology
MH  - Diabetic Angiopathies/*prevention & control
MH  - Diabetic Nephropathies/pathology/*prevention & control
MH  - Glomerular Mesangium/pathology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Polymerase Chain Reaction
MH  - Serum Albumin/metabolism
MH  - Streptozocin
EDAT- 2007/05/03 09:00
MHDA- 2007/09/22 09:00
CRDT- 2007/05/03 09:00
PHST- 2007/05/03 09:00 [pubmed]
PHST- 2007/09/22 09:00 [medline]
PHST- 2007/05/03 09:00 [entrez]
AID - db06-1593 [pii]
AID - 10.2337/db06-1593 [doi]
PST - ppublish
SO  - Diabetes. 2007 Sep;56(9):2371-9. doi: 10.2337/db06-1593. Epub 2007 May 1.