Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury

Am J Pathol. 2006 Aug;169(2):372-87. doi: 10.2353/ajpath.2006.060043.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Actins / metabolism
  • Animals
  • Antibodies / immunology
  • CX3C Chemokine Receptor 1
  • Chemokine CX3CL1
  • Chemokines, CX3C / genetics
  • Fibrosis
  • Kidney / cytology
  • Kidney / pathology
  • Kidney Function Tests
  • Macrophages / cytology
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephritis, Interstitial / pathology*
  • Neutralization Tests
  • Platelet-Derived Growth Factor / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / deficiency
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Reperfusion Injury*
  • Time Factors
  • Transforming Growth Factor beta / metabolism

Substances

  • Actins
  • Antibodies
  • CX3C Chemokine Receptor 1
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • Cx3cr1 protein, mouse
  • Membrane Proteins
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Receptors, Chemokine
  • Transforming Growth Factor beta