Role for macrophage migration inhibitory factor in peritoneal fibrosis

巨噬细胞迁移抑制因子在腹膜纤维化中的作用

• 批准号: 17590813
• 负责人: SASAKI Satoshi
• 金额: $ 2.24万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590813/
• 关键词: migration inhibitory factor; peritoneal fibrosis; pro-inflammatory cytokine; 被嚢性腹膜硬化症; TNF-α

MIF is known as a pro-inflammatory cytokine and recent studies have revealed multi-functional property of this cytokine in cell proliferation, fibrosis and angiogenesis. We investigated MIF' s role in PF by studying an experimental model of PF in MIF-knockout (MIF-/-) mice. Methods. PF was induced by intra-peritoneal infusion of chlorhexidine gluconate (CG) in wild type (WT) or MIF-/-mice from Balb/c origin. The mice were sacrificed at weeks 1-4 from the start of infusion and examined histologically. We also attempted to clarify whether an intraperitoneal injection of anti-MIF antibody could attenuate PF. The expression of MIF, TNF-α and the macrophage infiltration were examined by immunohistochemistry. Results. The peritoneum in WT showed progressive thickening by CG infusion. From week 2, peritoneal thickening was significantly inhibited in MIF-/-mice as compared with WT. The thickening was also inhibited by anti-MIF antibody treatment. Thickened peritoneum in WT showed massive infiltration of macrophages positive for F4/80 antigen. In MIF-/-mice, the infiltration is significantly inhibited. Ultrastructurally WT demonstrated mesothelial cells showing degenerative changes of the shape and sparse microvilli. In contrast, mesothelial cells in MIF-/-mice exhibited normal-shaped and extensive formation of thick microvilli. By immunohistochemical analysis, mesothelial cells and submesothelial compact zone in WT showed an increase in MIF expression at week 1. The expression further increased in the mesothelial layer supposed to be regenerated epithelium at week 3. TNF-α was strongly co-expressed with MIF in the mesothelium and compact zone in WT; however, the MIF-/- mice showed a significant decrease in TNF-α expression. Conclusions. Our data suggest that MIF plays important roles in PF. MIF inhibition may protect the progression of PF by the anti-inflammatory effect and also by the inhibition of mesothelial damage.

MIF 被称为促炎细胞因子，最近的研究揭示了这种细胞因子在细胞增殖、纤维化和血管生成中的多功能特性，我们通过研究 MIF 敲除中的 PF 实验模型（MIF -/）来研究 MIF 在 PF 中的作用。 -) 方法通过向野生型 (WT) 或来自 Balb/c 的 MIF-/- 小鼠腹腔注射葡萄糖酸氯己定 (CG) 诱导 PF。在输注开始后第 1-4 周处死小鼠并进行组织学检查，以阐明腹膜内注射抗 MIF 抗体是否可以减弱 PF、TNF-α 的表达和巨噬细胞浸润。通过免疫组织化学检查结果显示，从第 2 周开始，WT 的腹膜逐渐增厚。与WT相比，MIF-/-小鼠的腹膜增厚也受到抑制。WT中增厚的腹膜​​显示F4/80抗原阳性的巨噬细胞的大量浸润。超微结构WT显示间皮细胞显示出形状的退行性改变和稀疏的微绒毛。 MIF-/-小鼠表现出正常形状和广泛形成的厚微绒毛。通过免疫组织化学分析，WT 中的间皮细胞和间皮下致密区在第 1 周显示 MIF 表达增加。在应该再生的间皮层中表达进一步增加。第 3 周的上皮细胞。在 WT 的间皮和致密区中，TNF-α 与 MIF 强烈共表达；然而，MIF-/-结论：小鼠中 TNF-α 表达显着降低，表明 MIF 抑制可通过抗炎作用和抑制间皮损伤来保护 PF 的进展。

项目成果

Glomerular localization of erythropoietin receptor mRNA and protein in neonatal and mature mouse kidney

• DOI: 10.1159/000084109
• 发表时间: 2005-01-01
• 期刊: NEPHRON EXPERIMENTAL NEPHROLOGY
• 作者: Echigoya, MH;Obikane, K;Sasaki, S
• 通讯作者: Sasaki, S

膜性腎症 小児 : ネフローゼ症候群のすべて(臨床 治療各論)

儿童膜性肾病：关于肾病综合征的一切（临床治疗详情）

• 发表时间: 2005
• 期刊: 腎と透析 59巻増刊
• 作者: Li B;Morioka T;Uchiyama M;Oite T;Katsuya K;佐々木 聡
• 通讯作者: 佐々木 聡

ループス腎炎 : 小児の治療指針(腎・尿路)

狼疮性肾炎：儿童治疗指南（肾脏/泌尿道）

• 发表时间: 2006
• 期刊: 小児科診療 69巻増刊
• 作者: Sakamoto H;Shimizu J;Horio H;Ueda R;Takahashi T;Mitsudomi T;Yatabe Y;Murakami H.;高田 實;Ohshimo S.;高田 實;Mitsuta K;佐々木 聡;Irifune K;服部 登;Obikane K;佐々木 聡
• 通讯作者: 佐々木 聡

Transgenic mice overexpressing macrophage migration inhibitory factor (MIF) exhibit high-turnover osteoporosis

• DOI: 10.1359/jbmr.060310
• 发表时间: 2006-06-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Onodera, Shin;Sasaki, Satoshi;Yasuda, Kazunori
• 通讯作者: Yasuda, Kazunori

Renal failure due to tubulointerstitial nephropathy in an infant with cranioectodermal dysplasia

• DOI: 10.1007/s00467-006-0031-8
• 发表时间: 2006-04-01
• 期刊: PEDIATRIC NEPHROLOGY
• 影响因子: 3
• 作者: Obikane, K;Nakashima, T;Sasaki, S
• 通讯作者: Sasaki, S