title: Fractalkine and its receptor, CX3CR1, upregulation in streptozotocin-induced diabetic kidneys.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan. grd1615@gr.ndmc.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Ryota
authors.initials: R
authors.lastname: Ikee
authors.forename: Noriaki
authors.initials: N
authors.lastname: Hemmi
authors.forename: Naomi
authors.initials: N
authors.lastname: Hyodo
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Saigusa
authors.forename: Tamehachi
authors.initials: T
authors.lastname: Namikoshi
authors.forename: Muneharu
authors.initials: M
authors.lastname: Yamada
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
mesh_terms: 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
chemical_list: 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