P2X7 Deficiency Attenuates Renal Injury in Experimental Glomerulonephritis

被引：109

作者：

Taylor, Simon R. J. ^{[1
]}

Turner, Clare M. ^{[4
]}

Elliott, James I. ^{[2
]}

McDaid, John

Hewitt, Reiko

Smith, Jennifer

Pickering, Matthew C. ^{[2
]}

Whitehouse, Darren L. ^{[6
]}

Cook, H. Terence ^{[3
]}

Burnstock, Geoffrey ^{[5
]}

Pusey, Charles D.

Unwin, Robert J. ^{[4
]}

Tam, Frederick W. K.

机构：

[1] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Imperial Coll Kidney & Transplant Inst, London W12, England

[2] Univ London Imperial Coll Sci Technol & Med, Dept Mol Genet & Rheumatol, Div Med, London W12, England

[3] Univ London Imperial Coll Sci Technol & Med, Dept Pathol, Div Invest Sci, London W12, England

[4] UCL, Ctr Nephrol, London, England

[5] UCL, Autonom Neurosci Ctr, London, England

[6] Inst Pharmaceut Discovery LLC, Dept Chem, Branford, CT USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2009年 / 20卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL CRESCENTIC GLOMERULONEPHRITIS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NEPHROTOXIC NEPHRITIS; MICE; EXPRESSION; CELLS; INFLAMMATION; PROGRESSION; INHIBITION;

D O I：

10.1681/ASN.2008060559

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

100201 [内科学]; 100221 [泌尿外科学];

摘要：

The P2X(7), receptor is a ligand-gated cation channel that is normally expressed by a variety of immune cells, including macrophages and lymphocytes. Because it leads to membrane blebbing, release of IL-1 beta, and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of inflammatory diseases. Although the P2X(7) receptor is usually not detectable in normal renal tissue, we previously reported increased expression of both mRNA and protein in mesangial cells and macrophages infiltrating the glomeruli in animal models of anti body-mediated glomerulonephritis. In this study, we used P2X(7)-knockout mice in the same experimental model of glomerulonephritis and found that P2X(7) deficiency was significantly renoprotective compared with wild-type controls, evidenced by better renal function, a striking reduction in proteinuria, and decreased histologic glomerular injury. In addition, the selective P2X(7) antagonist A-438079 prevented the development of antibody-mediated glomerulonephritis in rats. These results support a proinflammatory role for P2X(7) in immune-mediated renal injury and suggest that the P2X(7) receptor is a potential therapeutic target.

引用

页码：1275 / 1281

页数：7

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