Macrophage as a therapeutic target for chronic kidney diseases

巨噬细胞作为慢性肾脏疾病的治疗靶点

• 批准号: 22591177
• 负责人: IKEZUMI Yohei
• 金额: $ 2.83万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591177/
• 关键词: 小児腎・泌尿器学; 慢性腎疾患; 活性化マクロファージ; M1; M2; 高脂血症; 線維化; 難治性ネフローゼ症候群; 難治性腎炎; ステロイド抵抗性ネフローゼ症群

Macrophage accumulation typically observed during progression of all kidney diseases and is potentially involved in the development of clinico-histopathological abnormalities observed as the disease progresses. These findings suggest that macrophages could be an important therapeutic target for chronic kidney diseases although their roles at the site of kidney lesion remain to be elucidated. We studied the mechanism of activated macrophage-mediated kidney injury using renal biopsy tissue, experimental model and culture system. Our studies on activated macrophages revealed that different macrophage phenotypes (M1 and M2) are involved in chronic glomerulonephritis with specific roles in different phases and lesions. The M1-activated macrophage, a pro-inflammatory phenotype, appeared to play a role in acute glomerular injury and was detected in active glomerular lesions such as cellular glomerular crescents and glomerular cell proliferations, and was suppressed by glucocorticoids. In contrast, the M2-activated phenotype, an anti-inflammatory phenotype, was more predominant in sites with chronic lesions such as glomerular sclerotic lesions and interstitial fibrosis, and was rather activated by glucocorticoids. Thus, macrophage phenotype-specific targeting, timing of treatment, and choice of therapeutic agents are vital in the prevention of macrophage-mediated renal injury.

巨噬细胞积累通常在所有肾脏疾病的进展过程中观察到，并且可能与疾病进展中观察到的临床组织病理学异常的发展有关。这些发现表明巨噬细胞可能是慢性肾脏疾病的重要治疗靶点，尽管它们在肾脏病变部位的作用仍有待阐明。我们采用肾活检组织、实验模型和培养系统研究活化巨噬细胞介导的肾损伤机制。我们对活化的巨噬细胞的研究发现，不同的巨噬细胞表型（M1和M2）参与慢性肾小球肾炎，在不同的阶段和病变中具有特定的作用。m1激活的巨噬细胞是一种促炎表型，似乎在急性肾小球损伤中发挥作用，并在活动性肾小球病变（如细胞肾小球新月形和肾小球细胞增殖）中检测到，并被糖皮质激素抑制。相比之下，m2激活表型，一种抗炎表型，在肾小球硬化病变和间质纤维化等慢性病变部位更为突出，并且更多地被糖皮质激素激活。因此，巨噬细胞表型特异性靶向、治疗时机和治疗药物的选择对于预防巨噬细胞介导的肾损伤至关重要。

项目成果

小児IgA腎症の高血圧合併例に関する組織学的検討

小儿IgA肾病并发高血压的组织学研究

• 发表时间: 2011
• 期刊: 小児高血圧研究会誌
• 作者: Inukai T;Kiyokawa N;Campana D;Coustan-Smith E;Kikuchi A;Kobayashi M;Takahashi H;Koh K;Manabe A;Kumagai M;Ikuta K;Hayashi Y;Tsuchida M;Sugita K;Ohara A.;篠原麻由ら;池住洋平,鈴木俊明,唐澤環,長谷川博也,金子詩子,内山聖
• 通讯作者: 池住洋平,鈴木俊明,唐澤環,長谷川博也,金子詩子,内山聖

Development of steroid-resistant pediatric nephrotic syndrome following prolonged steroid therapy is associated with alternative macrophage activation．

长期类固醇治疗后出现类固醇抵抗性小儿肾病综合征与替代性巨噬细胞激活有关。

• 发表时间: 2012
• 作者: Shiba N;Kanazawa T;Park MJ;Okuno H;Tamura K;Tsukada S;Hayashi Y;Arakawa H.;池住洋平
• 通讯作者: 池住洋平

慢性糸球体腎炎の治療になぜ免疫抑制薬を併用するのか？

为什么要联合使用免疫抑制剂来治疗慢性肾小球肾炎？

• 发表时间: 2012
• 作者: Mizushima Y;Taki T;Shimada A;Yui Y;Hiraumi Y;Matsubara H;Watanabe M;Watanabe K;Kamitsuji Y;Hayashi Y;Tsukimoto I;Kobayashi R;Horibe K;Tawa A;Nakahata T;Adachi S.;池住洋平
• 通讯作者: 池住洋平

腎血管性高血圧.50の典型例で学ぶ小児の腎泌尿器疾患(金子一成編)

从肾血管性高血压典型病例看儿童肾脏和泌尿系统疾病（金子一成主编）

• 发表时间: 2011
• 作者: Hayabuchi Y;Inoue M;Sakata M;Kagami S;池住洋平
• 通讯作者: 池住洋平

慢性腎炎(病態生理).小児のネフローゼと腎炎.小児科臨床ピクシス(五十嵐隆総編集)

慢性肾炎（病理生理学）。小儿肾病和肾炎（总编辑，五十岚隆）。

• 发表时间: 2010
• 作者: 佐野弘純;他;池住洋平
• 通讯作者: 池住洋平