title: Fractalkine and its receptor, CX3CR1, promote hypertensive interstitial fibrosis in the kidney.
abstract: Hypertension promotes and escalates kidney injury, including kidney fibrosis. Fractalkine/CX3CL1 is a unique chemokine that works as a leukocyte chemoattractant and an adhesion molecule. Recently, fractalkine/CX3CL1 has been reported to promote tissue fibrosis via its cognate receptor, CX3CR1. However, the involvement of the fractalkine-CX3CR1 axis in the pathogenesis of hypertensive kidney fibrosis remains unclear. The impacts of the fractalkine-CX3CR1 axis on hypertensive kidney fibrosis were investigated in a deoxycorticosterone acetate (DOCA)-salt hypertensive model in CX3CR1-deficient mice, which were sacrificed on day 28. The blood pressure levels were similarly elevated in both CX3CR1-/- C57BL/6 and wild-type C57BL/6 mice. Fractalkine and CX3CR1 were upregulated in kidneys that were damaged by hypertension. Deficiency in CX3CR1 inhibited kidney fibrosis, as evidenced by a decrease in the presence of interstitial fibrotic area detected by type I collagen in Mallory-Azan staining, concomitant with the downregulation of transforming growth factor (TGF)-β(1) and type I procollagen mRNA expression in damaged kidneys. The CX3CR1 blockade also decreased the number of infiltrating F4/80-positive macrophages in damaged kidneys. These results suggest that the fractalkine-CX3CR1 axis contributes to kidney fibrosis in a hypertensive mouse model, possibly by the upregulation of macrophage infiltration and the expression of TGF-β(1) and type I collagen.
authors: Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. ts243133@ton21.ne.jp
authors: Kazuaki
authors: K
authors: Shimizu
authors: Kengo
authors: K
authors: Furuichi
authors: Norihiko
authors: N
authors: Sakai
authors: Kiyoki
authors: K
authors: Kitagawa
authors: Kouji
authors: K
authors: Matsushima
authors: Naofumi
authors: N
authors: Mukaida
authors: Shuichi
authors: S
authors: Kaneko
authors: Takashi
authors: T
authors: Wada
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000502:physiology*; D003900:Desoxycorticosterone; D005355:Fibrosis; D006973:Hypertension / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000502:physiology*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000032:analysis
chemical_list: D000943:Antigens, Differentiation; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D053773:Transforming Growth Factor beta1; C036763:monocyte-macrophage differentiation antigen; D003900:Desoxycorticosterone