Study of lysosomal storage disease-intracellular signaling and apoptosis

溶酶体贮积病-细胞内信号传导与细胞凋亡的研究

• 批准号: 11670760
• 负责人: INUI Koji
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670760/
• 关键词: Farber disease; Subcutaneous nodules; apoptosis; Ceramide; MCP-1; TGF-β; 炎症性サイトカイン; RT-PCR法; リソソーム病; 脂質蓄積

Farber disease is a rare inherited metaboric disorder, in which cardinal symptom is ceramide enriched subcutaneous nodules due to a deficiency of lysosomal acid ceramidase. I examined expressed genes in nodules from a patient and macrophage like cell lines induced by cell permeable ceramide, to elucidate the roll of ceramide in cell signaling mechanism. From these results, I deduced that ceramide accumulation induced macrophage infiltration in nodules through the up-regulation of the MCP-1 (macrophage chemoattractant protein 1) gene expression and also induced TGF-β gene expression. These results partly explain the pathogenesis of nodule formation and macrophage infiltration.

Farber病是一种罕见的遗传性代谢性疾病，其主要症状是由于溶酶体酸性神经酰胺酶缺乏而导致皮下结节富含神经酰胺。为了阐明神经酰胺在细胞信号转导机制中的作用，我检测了细胞通透性神经酰胺诱导的结节和巨噬细胞样细胞系中的表达基因。根据这些结果，我推测神经酰胺的堆积通过上调巨噬细胞趋化蛋白1(MCP-1)基因的表达而诱导巨噬细胞在结节内的浸润，并诱导转化生长因子-β基因的表达。这些结果部分解释了结节形成和巨噬细胞浸润的发病机制。

项目成果

Inui K.,Miyagawa H.et al.: "Remission of progressive multifocal・・・・"Brain & Development. 21. 416-419 (1999)

Inui K.、Miyakawa H. 等人：“渐进性多焦点的缓解……”《大脑与发育》21. 416-419 (1999)。

乾幸治: "今日の小児治療指針-Niemann-Pick病"医学書院. 147-148 (2000)

Koji Inui：“当今的儿科治疗指南 - 尼曼-匹克病”Igaku Shoin 147-148 (2000)。

Inui et al.: "A case of chronic infantile …"Brain Der. 22. 47-49 (2000)

Inui 等人：“慢性婴儿病例……”Brain Der. 22. 47-49 (2000)

Tsukamoto et al.: "Enhanced expression of recominant ‥‥"Gene Ther.. 6. 1331-1335 (1999)

Tsukamoto 等人：“重组‥‥的增强表达”Gene Ther.. 6. 1331-1335 (1999)

Fu L, Inui K, Nishigaki T, Tatsumi N, Tsukamoto H, Kokubu C, Muramatsu T, Okada S: "Molecular heterogeneity of Krabbe disease."J Inher Metab Dis. 22. 155-162 (1999)

Fu L、Inui K、Nishigaki T、Tatsumi N、Tsukamoto H、Kokubu C、Muramatsu T、Okada S：“克拉伯病的分子异质性。”J Inher Metab Dis。