Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys.
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.
Kikuchi
Yuichi
Y
Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan. grd1615@gr.ndmc.ac.jp
Ikee
Ryota
R
Hemmi
Noriaki
N
Hyodo
Naomi
N
Saigusa
Takamitsu
T
Namikoshi
Tamehachi
T
Yamada
Muneharu
M
Suzuki
Shigenobu
S
Miura
Soichiro
S
D000818:Animals; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015728:Receptors, HIV / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV