Analysis of GADD34 function in aging, nutrient control and wound healing

GADD34在衰老、营养控制和伤口愈合中的功能分析

• 批准号: 22700691
• 负责人: ITO Sachiko
• 金额: $ 2.5万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700691/
• 关键词: GADD34; mTORシグナル; 絶食ストレス; 創傷治癒; 栄養欠乏ストレス; TORシグナル伝達系; 老化; 栄養制御

In this study, we analyzed the function of Growth arrest and DNA damage protein 34 (GADD34) in aging, nutrient deficient-stress and wound healing by using GADD34 Knock out(KO)mice. Starvation induced the expression of GADD34 in the liver. GADD34 bound to and dephosphorylated pTSC2. The dephosphorylation of pTSC2 leads to the suppression of mTOR, which isa potent inhibitor of autophagy. The starvation-induced GADD34 suppressed mTOR and induced autophagy. In wound healing, the rate of wound closure was faster in GADD34 KO MEFs (mouse embryonic fibroblasts) than in wild type(WT) MEFs. WT mice expressed higher amounts of myosin IIA in migrating macrophages and myofibroblasts than in GADD34 KO mice. These results indicate that GADD34 negatively regulates cell migration in wound healing via expression of Myosin IIA.

本研究以生长停滞和DNA损伤蛋白34（Growth arrest and DNA damage protein 34，GADD 34）基因敲除（Knock out，KO）小鼠为研究对象，分析了GADD 34在衰老、营养缺乏应激和创伤愈合中的作用。饥饿诱导肝脏中GADD 34的表达。GADD 34结合到pTSC 2并使其去磷酸化。pTSC 2的去磷酸化导致mTOR的抑制，mTOR伊萨自噬的有效抑制剂。饥饿诱导的GADD 34抑制mTOR并诱导自噬。在伤口愈合中，GADD 34 KO MEF（小鼠胚胎成纤维细胞）中的伤口闭合速率比野生型（WT）MEF中更快。WT小鼠在迁移的巨噬细胞和肌成纤维细胞中表达的肌球蛋白IIA量高于GADD 34 KO小鼠。这些结果表明，GADD 34通过肌球蛋白IIA的表达负调节伤口愈合中的细胞迁移。

项目成果

GADD34 suppresses wound healing by upregulating expression of myosin IIA

• DOI: 10.1007/s11248-009-9347-z
• 发表时间: 2010-08
• 期刊: Transgenic Research
• 影响因子: 3
• 作者: C. Tanaka;S. Ito;N. Nishio;Y. Kodera;H. Sakurai;Haruhiko Suzuki;A. Nakao;K. Isobe

GADD34 regulates the LPS-induced cytokine production via TSC-mTOR signaling pathway

GADD34 通过 TSC-mTOR 信号通路调节 LPS 诱导的细胞因子产生

• 发表时间: 2011
• 作者: 伊藤佐知子;西尾尚美;鈴木治彦;磯部健一
• 通讯作者: 磯部健一