RGD Reference Report - Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys. - Rat Genome Database

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Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys.

Authors: Kikuchi, Y  Ikee, R  Hemmi, N  Hyodo, N  Saigusa, T  Namikoshi, T  Yamada, M  Suzuki, S  Miura, S 
Citation: Kikuchi Y, etal., Nephron Exp Nephrol. 2004;97(1):e17-25.
RGD ID: 4891992
Pubmed: PMID:15153757   (View Abstract at PubMed)
DOI: DOI:10.1159/000077594   (Journal Full-text)

BACKGROUND: Fractalkine is induced on activated endothelial cells and promotes strong adhesion of T cells and monocytes via its receptor CX3CR1. In kidney, fractalkine expression might be induced by high shear stress and play an important role in prolonged glomerular diseases. We examined whether fractalkine and CX3CR1 upregulation are found in streptozotocin-induced diabetic kidneys. METHODS: Diabetic rats were randomized to receive an angiotensin-converting enzyme inhibitor (temocapril), aminoguanidine or no treatment. Reverse transcription-competitive polymerase chain reaction, Western blot analysis and immunohistochemistry were used. RESULTS: At 4 weeks, fractalkine and CX3CR1 mRNA expression in diabetic kidneys increased compared with that in controls. Fractalkine staining in diabetic kidneys was clearly detected, along with glomerular capillary lumen and peritubular capillaries. A few CX3CR1 positive cell infiltration in diabetic glomeruli were found. Treatment with temocapril or aminoguanidine did not affect these changes. At 8 weeks, fractalkine and CX3CR1 mRNA expression in untreated diabetic kidneys markedly increased compared with that in controls. Membrane-anchored fractalkine protein expression in untreated diabetic rats also increased. The increased expression was suppressed by the treatment with temocapril and aminoguanidine. Increased CX3CR1-positive cell infiltration in diabetic glomeruli was also inhibited by both treatments. Some CX3CR1-positive cells were ED3 positive. CONCLUSIONS: Fractalkine and CX3CR1 upregulation were demonstrated in an early stage of diabetic kidney. These upregulation, as well as urinary albumin excretion, were suppressed by treatments with temocapril and aminoguanidine for 8 weeks. These findings suggest that fractalkine expression and CX3CR1-positive cell infiltration in diabetic kidneys might play an important role for progression of diabetic nephropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOCx3cl1 (Rattus norvegicus)4891992; 4891992mRNA:increased expression:kidneyRGD 
Experimental Diabetes Mellitus  ISOCx3cr1 (Rattus norvegicus)4891992; 4891992mRNA:increased expression:kidneyRGD 
Experimental Diabetes Mellitus  IEP 4891992; 4891992mRNA:increased expression:kidneyRGD 

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)


Additional Information