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

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）的伤口闭合速度比野生型（WT）MEF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。

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.