Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury.
Transient renal ischemia induces both inflammatory and fibrotic processes and is a major cause of acute and chronic renal insufficiency. Study of ischemia-reperfusion injury in gene-targeted mice has identified multiple factors responsible for inflammation, whereas mechanisms underlying fibrosis remain poorly defined. Here we demonstrate by both gene inactivation and target protein blockade that a single chemokine receptor subtype, the fractalkine receptor CX3CR1, is able to reduce both inflammation and fibrosis after ischemia-reperfusion injury in the mouse, leading to partially preserved renal function after injury. The mechanism involves selective effects in the outer medulla, including reduced accumulation of macrophages and reduced expression of the macrophage and platelet-derived fibrogenic protein platelet-derived growth factor-B. CX3CR1 is the first chemokine receptor shown to contribute to fibrogenesis in renal ischemia-reperfusion injury.
Furuichi
Kengo
K
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N113, Bethesda, MD 20892-9000, USA.
Gao
Ji-Liang
JL
Murphy
Philip M
PM
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics; D005355:Fibrosis; D007668:Kidney / Q000166:cytology / Q000473:pathology; D007677:Kidney Function Tests; D008264:Macrophages / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000473:pathology*; D009500:Neutralization Tests; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000199:Actins; D000906:Antibodies; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta