A novel strategy to minimize mTOR-induced autophagy to pancreatic islet beta cells

一种最小化 mTOR 诱导的胰岛 β 细胞自噬的新策略

• 批准号: 20591524
• 负责人: ITO Toshinori
• 金额: $ 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591524/
• 关键词: 膵島移植; 1型糖尿病; オートファジー; 長期成績; mTOR阻害剤; 3-MA; I型糖尿病; オートファージ; mTOR inhibitor r; mTOR inhibitor

Mammalian target of rapamycin (mTOR) inhibitor has extensively used in clinical islet transplantation to prevent the graft rejection. Recently, mTOR inhibitor has also reported to induce autophagy to various kinds of cell lines. Autophagy is an essential, homeostatic process by which cells break down their own components. However, its role on pancreatic islets has not been thoroughly understood. In this study we demonstrated that both in vitro and in vivo, rapamycin treatment induced autophagy to islets. Furthermore, addition of autophagy inhibitor resulted in better graft outcome. These results suggest that rapamycin with autophagy inhibitor would be an ideal combination to prevent graft rejection without autophagy induction.

哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂已广泛应用于临床胰岛移植，以预防移植排斥反应。最近，mTOR抑制剂也报道诱导各种细胞系的自噬。自噬是细胞分解自身成分的一个重要的稳态过程。然而，其对胰岛的作用尚未完全了解。在这项研究中，我们证明了在体外和体内，雷帕霉素治疗诱导胰岛自噬。此外，添加自噬抑制剂导致更好的移植结果。这些结果表明，雷帕霉素与自噬抑制剂将是一种理想的组合，以防止移植排斥反应，而不诱导自噬。

项目成果

In Vitro and in Vivo Prevention of Human CD8+ CTL‐Mediated Xenocytotoxicity by Pig c‐FLIP Expression in Porcine Endothelial Cells

通过猪内皮细胞中的猪 c-FLIP 表达在体外和体内预防人 CD8+ CTL 介导的异细胞毒性

• DOI: 10.1111/j.1600-6143.2007.02077.x
• 发表时间: 2008
• 期刊: American Journal of Transplantation
• 影响因子: 8.8
• 作者: M. Tanemura;A. Saga;K. Kawamoto;T. Deguchi;T. Machida;T. Nishida;Y. Sawa;T. Ito
• 通讯作者: T. Ito

異種膵島移植療法の臨床応用に向けた先端研究

异种胰岛移植治疗临床应用进展研究

• 发表时间: 2009
• 作者: 種村匡弘;伊藤壽記;永野浩昭;出口貴司;町田智彦;小林省吾;丸橋繁;武田裕;北川透;堂野恵三;門田守人;森正樹;土岐祐一郎
• 通讯作者: 土岐祐一郎

GBP2 mRNA in peripheral blood leukocytes of liver transplant recipients as a marker for acute cellular rejection.

肝移植受者外周血白细胞中的 GBP2 mRNA 作为急性细胞排斥的标志物。

• 发表时间: 2009
• 期刊: Transplant int. 23(4)
• 作者: Kobayashi S;Marubashi S;Hama N;Asaoka T;Eguchi H;Takeda Y;Tanemura M;Doki Y;Mori M.
• 通讯作者: Mori M.

Hybrid islet transplantation with marginal islet mass and adipose tissue-derived stem cells can elicit long-term islet graft survival and support normoglycemia in diabetic mice.

具有边缘胰岛质量和脂肪组织来源的干细胞的混合胰岛移植可以引起长期胰岛移植物存活并支持糖尿病小鼠的正常血糖。

• 发表时间: 2010
• 作者: Y.Ohmura;M.Tanemura;T.Machida;T.Deguchi;H.Wada;S.Kobayashi;S.Marubashi;H.Eguchi;Y.Takeda;N.Kawaguchi;N.Matsuura;T.Ito;H.Nagano;Y.Doki;M.Mori
• 通讯作者: M.Mori

MUC1, remodeled to express α-gal epitopes immune-based therapy can elicit both significant prolonged survival and effective antibody production against multiple tumor-associated antigens.

MUC1 被重构以表达 α-gal 表位，基于免疫的治疗可以显着延长生存期，并有效产生针对多种肿瘤相关抗原的抗体。

• 发表时间: 2010
• 作者: Tanemura M;Deguchi T;Miyoshi E;Nagano H;Ohmura Y;Machida T;Wada H;Kobayashi S;Marubash S;Eguchi H;Takeda Y;Ito T;Mori M;Doki Y
• 通讯作者: Doki Y