Involvement of bone marrow-derived fibrocyte in the pathogenesis of pulmonary fibrosis and the effect of newly developed anti-fibrotic agents

骨髓源性纤维细胞参与肺纤维化发病机制及新开发的抗纤维化药物的作用

• 批准号: 23591163
• 负责人: AZUMA Arata
• 金额: $ 3.33万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591163/
• 关键词: 特発性肺線維症; 線維細胞; ピルフェニドン; fibrocyte

Bone marrow-derived fibrocytes reportedly play important roles in the pathogenesis of idiopathic pulmonary fibrosis. Pirfenidone (PFD) is an anti-fibrotic agent; however, its effects on fibrocytes have not been investigated. The aim of this study was to investigate whether PFD inhibits fibrocyte pool size in the lungs of bleomycin (BLM)-treated mice. To achieve this, C57BL/6 mice were treated with BLM and PFD was administered. Fibrocyte pool size in BLM-treated mice lungs was attenuated by PFD. This was also observed in a therapeutic setting. Increased chemokine (CC motif) ligand-2 (CCL2) and CCL12 production in BLM-treated mouse lungs was significantly attenuated by PFD. Fibrocyte migration toward CCL2 and chemokine (CC motif) receptor-2 expression on fibrocytes were significantly inhibited by PFD in vitro. Fibrocyte inhibition is considered a mechanism of anti-fibrotic action of PFD.

骨髓源性纤维细胞在特发性肺纤维化的发病机制中起重要作用。吡非尼酮（PFD）是一种抗纤维化药物;然而，尚未研究其对纤维细胞的影响。本研究的目的是调查PFD是否抑制博莱霉素（BLM）处理小鼠肺中纤维细胞池的大小。为了实现这一点，用BLM处理C57 BL/6小鼠并施用PFD。在BLM处理的小鼠肺中的纤维细胞池的大小被PFD减弱。在治疗环境中也观察到了这一点。在BLM处理的小鼠肺中增加的趋化因子（CC基序）配体-2（CCL 2）和CCL 12的产生被PFD显著减弱。在体外，PFD可显著抑制纤维细胞向CCL 2的迁移和纤维细胞上趋化因子受体（CC基序）的表达。纤维细胞抑制被认为是PFD抗纤维化作用的机制。

项目成果

Pirfenidone Inhibits Bone Marrow-Derived Fibrocytes Influx Into The Lungs In Bleomycin-Induced Murine Pulmonary Fibrosis

吡非尼酮抑制博来霉素诱导的小鼠肺纤维化中骨髓源性纤维细胞流入肺部

• 发表时间: 2013
• 作者: Minoru Inomata;Koichiro Kamio;Kuniko Matsuda;Nariaki Kokuho;Yukiko Miura;Kazue Fujita;Yoshinobu Saito;Akihiko Gemma;Arata Azuma
• 通讯作者: Arata Azuma

ブレオマイシン誘発肺障害モデルマウスにおけるピルフェニドンの骨髄由来fibrocyte抑制効果に関する検討

吡非尼酮对博莱霉素肺损伤模型小鼠骨髓源性纤维细胞抑制作用的研究

• 发表时间: 2013
• 作者: 猪俣稔;神尾孝一郎;松田久仁子;國保成暁;根井貴仁;三浦由記子;藤田和恵;齋藤好信;弦間昭彦;吾妻安良太
• 通讯作者: 吾妻安良太