Fractalkine and its receptor, CX3CR1, promote hypertensive interstitial fibrosis in the kidney
Fractalkine and its receptor, CX3CR1, promote hypertensive interstitial fibrosis in the kidney
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DOI：
10.1038/hr.2011.23
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Wada, Takashi
中科院分区：
文献类型：
--
作者：
Shimizu, Kazuaki;Furuichi, Kengo;Wada, Takashi
高血压促进和加剧肾损伤，包括肾纤维化。Fractalkine/CX 3CL 1是一种独特的趋化因子，作为白细胞化学引诱物和粘附分子发挥作用。最近，已经报道了fractalkine/CX 3CL 1通过其同源受体CX 3CR 1促进组织纤维化。然而，Fractalkine-CX 3CR 1轴在高血压肾纤维化的发病机制中的参与仍不清楚。在CX 3CR 1缺陷小鼠的醋酸脱氧皮质酮（DOCA）-盐高血压模型中研究了Fractalkine-CX 3CR 1轴对高血压肾纤维化的影响，这些小鼠在第28天处死。在CX 3CR 1/C57 BL/6和野生型C57 BL/6小鼠中，血压水平相似地升高。Fractalkine和CX 3CR 1在高血压损伤的肾脏中上调。CX 3CR 1缺乏可抑制肾纤维化，如Mallory-Azan染色中I型胶原检测到的间质纤维化面积减少所证明的，伴随着受损肾脏中转化生长因子（TGF）-β（1）和I型前胶原mRNA表达的下调。CX 3CR 1阻断还减少了受损肾脏中浸润的F4/80阳性巨噬细胞的数量。这些结果表明，在高血压小鼠模型中，Fractalkine-CX 3CR 1轴可能通过上调巨噬细胞浸润以及TGF-β 1和I型胶原的表达而促进肾纤维化。高血压研究（2011）34，747-752; doi：10.1038/hr.2011.23; 2011年3月31日在线发表
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)-beta(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-beta(1) and type I collagen. Hypertension Research (2011) 34, 747-752; doi:10.1038/hr.2011.23; published online 31 March 2011