Wada T, Sakai N, Matsushima K, Kaneko S
Division of Blood Purification, Department of Disease Control and Homeostasis, Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan.
Kidney Int. 2007 Aug;72(3):269-73. doi: 10.1038/sj.ki.5002325. Epub 2007 May 9.
Fibrocytes are supposed to be a circulating connective tissue cell progenitor, which consists of a novel population of peripheral blood cells. This distinct population of blood-borne cells shares markers of leukocytes as well as mesenchymal cells. Accumulating evidence indicates that fibrosis is characteristic of progressive chronic kidney diseases of any etiologies, resulting in kidney failure. We have uncovered that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to kidney fibrosis induced by unilateral ureteral obstruction in mice. In addition, the blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced kidney fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in macrophage recruitment along with reduced renal transcripts of monocyte chemoattractant protein-1 (MCP-1/CCL2). These findings suggest that fibrocytes dependent on CCL21/CCR7 signaling pathways contribute to the pathogenesis of kidney fibrosis, thereby providing that regulating fibrocytes may provide a novel therapeutic benefit for kidney fibrosis.
纤维细胞被认为是一种循环的结缔组织细胞祖细胞,由一群新型外周血细胞组成。这群独特的血源性细胞兼具白细胞和间充质细胞的标志物。越来越多的证据表明,纤维化是任何病因的进行性慢性肾脏病的特征,最终导致肾衰竭。我们发现,CCR7阳性纤维细胞会响应二级淋巴组织趋化因子(SLC/CCL21)迁移至肾脏,并促进小鼠单侧输尿管梗阻诱导的肾纤维化。此外,抗CCL21抗体对CCL21/CCR7信号的阻断减轻了肾纤维化,这在CCR7基因敲除小鼠的纤维化减轻中得到证实,同时巨噬细胞募集减少,单核细胞趋化蛋白-1(MCP-1/CCL2)的肾转录本也减少。这些发现表明,依赖CCL21/CCR7信号通路的纤维细胞促成了肾纤维化的发病机制,从而提示调节纤维细胞可能为肾纤维化提供一种新的治疗益处。