RGD Reference Report - Expression of CX3CL1/fractalkine by mesangial cells in vitro and in acute anti-Thy1 glomerulonephritis in rats. - Rat Genome Database

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Expression of CX3CL1/fractalkine by mesangial cells in vitro and in acute anti-Thy1 glomerulonephritis in rats.

Authors: Chen, YM  Hu-Tsai, MI  Lin, SL  Tsai, TJ  Hsieh, BS 
Citation: Chen YM, etal., Nephrol Dial Transplant. 2003 Dec;18(12):2505-14.
RGD ID: 4891995
Pubmed: PMID:14605272   (View Abstract at PubMed)

BACKGROUND: Mesangial cells (MCs) can promote glomerular macrophage accumulation in glomerulonephritis through production of a variety of chemokines. This study investigated the potential of MCs to synthesize CX3CL1/fractalkine, a CX3C chemokine, both in vitro and in acute anti-Thy1 glomerulonephritis in rats. METHODS: Anti-Thy1 glomerulonephritis was induced in Wistar rats by a single injection of mouse anti-rat Thy1.1 antibody intravenously. Glomerular mRNAs for CX3CL1/fractalkine, CCL2/monocyte chemoattractant protein (MCP)-1, and their cognate receptors, CX3CR1 and CCR2, were determined by northern blot analysis or reverse-transcription polymerase chain reaction. CX3CL1/fractalkine mRNA and protein expression in vivo was localized by in situ hybridization and immunohistochemistry. Monocytes/macrophages and activated MCs were detected by immunohistochemistry. Regulation of CX3CL1/fractalkine expression in cultured MCs was determined by northern and western blot analysis. RESULTS: After induction of anti-Thy1 disease, glomerular CX3CL1/fractalkine mRNA was significantly up-regulated, peaking at 2 h and sustaining into day 5 of the nephritis. A corresponding increase in urinary CX3CL1/fractalkine protein was evident after day 1 of the nephritis, but became more prominent during the MC proliferative phase (days 3-5). Meanwhile, induction of glomerular CCL2/MCP-1 mRNA and urinary CCL2/MCP-1 protein occurred within 24 h, and was barely detectable after day 3 of the nephritis. Urinary CCL2/MCP-1, but not CX3CL1/fractalkine, correlated with glomerular macrophage accumulation (r = 0.936, P<0.01) and glomerular CCR2 mRNA expression (r = 0.965, P<0.01). In contrast, only urinary CX3CL1/fractalkine coincided temporally to glomerular mRNA for CX3CR1 (r = 0.809, P < 0.01). Combined in situ hybridization and immunohistochemistry revealed that activated MCs were a major source for CX3CL1/fractalkine mRNA and protein during days 3-5 of the nephritis. Incubation of cultured MCs with tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, platelet-derived growth factor (PDGF)-AB or basic fibroblast growth factor (bFGF) significantly up-regulated CX3CL1/fractalkine mRNA and protein expression. This cytokine- and growth factor-stimulated CX3CL1/fractalkine expression could be abolished by the nuclear factor-kappaB inhibitors, curcumin and MG132. CONCLUSIONS: Our data demonstrate that activated MCs are a source for the augmented glomerular CX3CL1/fractalkine expression during the proliferative phase of acute anti-Thy1 glomerulonephritis. Up-regulation of MC CX3CL1/fractalkine by TNF-alpha, IL-1beta, PDGF-AB and bFGF is mediated, at least in part, via the nuclear factor-kappaB signalling pathway. The differential expression of CCL2/MCP-1 and CX3CL1/fractalkine may sequentially recruit distinct subsets of monocytes to the glomerulus during acute anti-Thy1 glomerulonephritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glomerulonephritis  ISOCx3cl1 (Rattus norvegicus)4891995; 4891995mRNA more ...RGD 
glomerulonephritis  ISOCx3cr1 (Rattus norvegicus)4891995; 4891995mRNA:increased expression:glomerulusRGD 
glomerulonephritis  IEP 4891995mRNA more ...RGD 
glomerulonephritis  IEP 4891995mRNA:increased expression:glomerulusRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cx3cl1  (C-X3-C motif chemokine ligand 1)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Mus musculus)
Cx3cl1  (C-X3-C motif chemokine ligand 1)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Homo sapiens)
CX3CL1  (C-X3-C motif chemokine ligand 1)
CX3CR1  (C-X3-C motif chemokine receptor 1)


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