Related Experiment Video
Updated: Jul 14, 2026
Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
Potential role of fractalkine receptor expression in human renal fibrogenesis
M J Koziolek1, H Schmid, C D Cohen
1Department of Nephrology and Rheumatology, Georg-August-University Goettingen, Robert-Koch-Street 40, D-37075 Goettingen, Germany. mkoziolek@med.uni-goettingen.de
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 CX(3)C receptor in human renal biopsies with interstitial fibrosis and from normal kidneys by real-time polymerase chain reaction (PCR) and immunohistochemistry. The CX(3)C 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 CX(3)C 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 CX(3)C 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 CX(3)C ligand led to a significant enhancement of migration, which was abrogated by pre-incubation with a blocking anti-CX(3)C receptor antibody. Our studies indicate that renal fibrosis is associated with the expression of CX(3)C receptors on human renal fibroblasts. The expression is induced by reactive oxygen species suggesting a role of oxidative stress.
Insights
This study found that CX3C receptor is upregulated in fibrotic kidneys, particularly on myofibroblasts. Oxidative stress, not inflammation, induces its expression, suggesting a role in kidney fibrosis progression.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Renal interstitial fibrosis is a key factor in progressive kidney disease.
- Chemokine/chemokine receptor signaling pathways are implicated in fibrosis development.
- The role of CX3C receptor in renal fibrosis remains unclear.
Purpose of the Study:
- To investigate the expression and role of the CX3C receptor in human renal interstitial fibrosis.
- To determine factors that regulate CX3C receptor expression in renal fibroblasts.
Main Methods:
- Real-time PCR and immunohistochemistry on human renal biopsies.
- In vitro studies on renal fibroblasts.
- Stimulation with CX3C ligand and reactive oxygen species.
Main Results:
- CX3C receptor is expressed on myofibroblasts, mononuclear cells, and tubular epithelial cells in fibrotic kidneys.
- CX3C receptor mRNA is significantly upregulated in fibrotic kidneys.
- Hydrogen peroxide, a reactive oxygen species, upregulates CX3C receptor expression in fibroblasts.
- CX3C ligand stimulation enhances fibroblast migration.
Conclusions:
- Renal fibrosis is associated with increased CX3C receptor expression on renal fibroblasts.
- Oxidative stress, rather than inflammatory or profibrotic cytokines, induces CX3C receptor expression.
- CX3C receptor signaling may contribute to the pathogenesis of renal fibrosis.
Related Concept Videos
01:41Non-Canonical Wnt Signaling Pathways
01:09Introduction to Fibroblasts