PMID- 21282555
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20211020
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 57
IP  - 3
DP  - 2011 Mar
TI  - Addition of angiotensin II type 1 receptor blocker to CCR2 antagonist markedly 
      attenuates crescentic glomerulonephritis.
PG  - 586-93
LID - 10.1161/HYPERTENSIONAHA.110.165704 [doi]
AB  - The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor 2 (CCR2) 
      pathway plays a critical role in the development of antiglomerular basement 
      membrane (anti-GBM) nephritis. We recently showed angiotensin II (Ang II) 
      infusion in rats activated MCP-1 and transforming growth factor-beta1 (TGF-beta1), 
      which in turn induced macrophage infiltration of renal tissues. This study was 
      performed to demonstrate that combination therapy with a CCR2 antagonist (CA) and 
      an Ang II type 1 receptor blocker (ARB) ameliorated renal injury in the anti-GBM 
      nephritis model. An anti-GBM nephritis rat model developed progressive 
      proteinuria and glomerular crescent formation, accompanied by increased 
      macrophage infiltration and glomerular expression of MCP-1, angiotensinogen, Ang 
      II, and TGF-beta1. Treatment with CA alone or ARB alone moderately ameliorated 
      kidney injury; however, the combination treatment with CA and ARB dramatically 
      prevented proteinuria and markedly reduced glomerular crescent formation. The 
      combination treatment also suppressed the induction of macrophage infiltration, 
      MCP-1, angiotensinogen, Ang II, and TGF-beta1 and reversed the fibrotic change in 
      the glomeruli. Next, primary cultured glomerular mesangial cells (MCs) stimulated 
      by Ang II showed significant increases in MCP-1 and TGF-beta1 expression. 
      Furthermore, cocultured model consisting of MCs, parietal epithelial cells, and 
      macrophages showed an increase in Ang II-induced cell proliferation and collagen 
      secretion. ARB treatment attenuated these augmentations. These data suggest that 
      Ang II enhances glomerular crescent formation of anti-GBM nephritis. Moreover, 
      our results demonstrate that inhibition of the MCP-1/CCR2 pathway with a 
      combination of ARB effectively reduces renal injury in anti-GBM nephritis.
FAU - Urushihara, Maki
AU  - Urushihara M
AD  - Department of Physiology and Hypertension and Renal Center of Excellence, Tulane 
      University Health Sciences Center, New Orleans, LA 70112-2699, USA.
FAU - Ohashi, Naro
AU  - Ohashi N
FAU - Miyata, Kayoko
AU  - Miyata K
FAU - Satou, Ryousuke
AU  - Satou R
FAU - Acres, Omar W
AU  - Acres OW
FAU - Kobori, Hiroyuki
AU  - Kobori H
LA  - eng
GR  - R01 DK072408/DK/NIDDK NIH HHS/United States
GR  - R01DK072408/DK/NIDDK NIH HHS/United States
GR  - R01 DK072408-01A1/DK/NIDDK NIH HHS/United States
GR  - P20 RR017659/RR/NCRR NIH HHS/United States
GR  - P20RR017659/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110131
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Analysis of Variance
MH  - Angiotensin II/*pharmacology
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Animals
MH  - Anti-Glomerular Basement Membrane Disease/*drug therapy/metabolism
MH  - Blood Pressure/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - Kidney/*drug effects/metabolism
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Receptors, CCR2/*antagonists & inhibitors
MH  - Renin-Angiotensin System/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta1/metabolism
PMC - PMC3048031
MID - NIHMS275398
EDAT- 2011/02/02 06:00
MHDA- 2011/04/16 06:00
PMCR- 2011/03/03
CRDT- 2011/02/02 06:00
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
PHST- 2011/03/03 00:00 [pmc-release]
AID - HYPERTENSIONAHA.110.165704 [pii]
AID - 10.1161/HYPERTENSIONAHA.110.165704 [doi]
PST - ppublish
SO  - Hypertension. 2011 Mar;57(3):586-93. doi: 10.1161/HYPERTENSIONAHA.110.165704. 
      Epub 2011 Jan 31.