Potential role of fractalkine receptor expression in human renal fibrogenesis

Abstract

The inhibition of several chemokine/chemokine receptors has been shown to reduce progressive renal interstitial fibrosis. In this study, we examined the expression of the CX3C receptor in human renal biopsies with interstitial fibrosis and from normal kidneys by real-time polymerase chain reaction (PCR) and immunohistochemistry. The CX3C receptor was not only detected in mononuclear, tubular epithelial, and dendritic cells but also in alpha-smooth muscle actin and vimentin-positive interstitial myofibroblasts in fibrotic kidneys. Real-time PCR indicated a significant upregulation of CX3C receptor mRNA in fibrotic kidneys compared with non-fibrotic nephropathies or donor biopsies. In renal fibroblasts in vitro, hydrogen peroxide increased the expression of the CX3C receptor, an increase that was inhibited by N-acetylcysteine and catalase. However, neither proinflammatory nor profibrotic cytokines resulted in this upregulation. Stimulation of fibroblasts by CX3C ligand led to a significant enhancement of migration, which was abrogated by pre-incubation with a blocking anti-CX3C receptor antibody. Our studies indicate that renal fibrosis is associated with the expression of CX3C receptors on human renal fibroblasts. The expression is induced by reactive oxygen species suggesting a role of oxidative stress.