Role of fibrocytes, a newly identified tone marrow-derived cells, in the pathogenesis of renal fibrosis

纤维细胞（一种新发现的骨髓来源细胞）在肾纤维化发病机制中的作用

• 批准号: 18590887
• 负责人: WADA Takashi
• 金额: $ 2.57万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590887/
• 关键词: fibre cote; chemokine; kidney; fibrosis; renin; angiotensin; angiotensin recentor; collagen; 慢性腎臓病; CCL21; SLC; CCR7

Fibrocytes are supposed to be a circulating connective tissue cell progenitor that 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). In addition, angiotensin receptor type 1 /type 2 signaling may contribute to the pathogenesis of renal fibrosis by at least two mechanisms: (1) by regulating the number of fibrocytes in bone marrow, and (2) by direct activation of fibrocytes via these two receptors. These findings suggest that fibrocytes dependent on CCL21/CCR7 signaling pathways and renin-angiotensin system 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，由一种新的外周血细胞群组成。这种独特的血源性细胞群具有白细胞和间充质细胞的标记。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疾病的特征，导致肾衰竭。我们发现ccr7阳性纤维细胞响应次级淋巴组织趋化因子（SLC/CCL21）迁移到肾脏，并参与小鼠单侧输尿管梗阻诱导的肾纤维化。此外，抗CCL21抗体阻断CCL21/CCR7信号通路可减少肾纤维化，CCR7缺失小鼠的纤维化减少，同时巨噬细胞募集减少，单核细胞趋化蛋白-1 （MCP-1/CCL2）的肾转录物减少，证实了这一点。此外，血管紧张素受体1 / 2型信号可能通过至少两种机制参与肾纤维化的发病机制：(1)通过调节骨髓中纤维细胞的数量，(2)通过这两种受体直接激活纤维细胞。这些发现表明，依赖于CCL21/CCR7信号通路和肾素-血管紧张素系统的纤维细胞参与了肾纤维化的发病机制，从而提供了调节纤维细胞可能为肾纤维化提供新的治疗益处。

项目成果

The role of chmokines in glomerulonephritis

趋化因子在肾小球肾炎中的作用

• 发表时间: 2008
• 期刊: Frontiers in Bioscience 13
• 作者: Wada T;et. al.
• 通讯作者: et. al.

Role of chmokines in renal ischemia

趋化因子在肾缺血中的作用

• 发表时间: 2008
• 期刊: Frontiers in Bioscience 13
• 作者: Furuichi K;Wada T;et. al.
• 通讯作者: et. al.

慢性腎臓病とケモカイン

慢性肾病和趋化因子

• 发表时间: 2007
• 作者: 和田隆志;他
• 通讯作者: 他

Lymphocyte migration to the kidney

淋巴细胞迁移至肾脏

• 发表时间: 2006
• 期刊: Lymphocyte Trafficking in Health and Disease
• 作者: Wada;T.;et. al.
• 通讯作者: et. al.

炎症・免疫担当細胞からみた腎臓病進展機序

从炎症和免疫细胞角度探讨肾脏疾病进展机制

• 发表时间: 2007
• 作者: 和田隆志;他
• 通讯作者: 他