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是一种促炎细胞因子，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基因敲除(MIF-/-)小鼠的PF实验模型，探讨了MIF在PF中的S作用。方法：研究方法。通过给野生型(WT)或Balb/c来源的MIF-/-小鼠腹腔注射葡萄糖酸氯己定(CG)诱发PF。于输液开始后1-4周处死小鼠，进行组织学检查。我们还试图阐明，腹腔注射抗MIF抗体是否可以减弱PF。免疫组织化学方法检测MIF、肿瘤坏死因子-α的表达及巨噬细胞的浸润情况。结果。注射CG后，WT组腹膜呈进行性增厚。从第2周开始，与WT相比，MIF-/-小鼠的腹膜增厚受到显著抑制。抗MIF抗体处理也能抑制细胞增厚。WT腹膜增厚可见大量F4/80抗原阳性的巨噬细胞浸润。在MIF-/-小鼠中，这种渗透明显受到抑制。超微结构WT显示间皮细胞形态退变，微绒毛稀疏。相反，MIF-/-小鼠的间皮细胞表现出正常形状和广泛的厚微绒毛形成。免疫组织化学分析显示，WT组间皮细胞和间皮下致密区在1周时表达增强，3周时在应为再生上皮的间皮层中表达进一步增强。在WT组间皮细胞和间皮下致密区中，肿瘤坏死因子-α与MIF强烈共表达，而在MIF-/-小鼠中，肿瘤坏死因子-α表达显著降低。结论。我们的数据表明，MIF在PF中起重要作用。MIF抑制可能通过抗炎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

Transgenic mice overexpressing macrophage migration inhibitory factor exhibit high-turn over osteoporosis

过度表达巨噬细胞迁移抑制因子的转基因小鼠表现出高周转骨质疏松症

• 发表时间: 2006
• 期刊: J Bone Miner Res 21
• 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;Onodera S
• 通讯作者: Onodera S