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

本研究以Gadd34基因敲除(KO)小鼠为研究对象，分析了生长停滞和DNA损伤蛋白34(Gadd34)在衰老、营养缺乏应激和创面愈合中的作用。饥饿诱导肝脏中Gadd34的表达。Gadd34与pTSC2结合并去磷酸化。PTSC2的去磷酸化导致mTOR的抑制，mTOR是一种有效的自噬抑制因子。饥饿诱导的Gadd34抑制mTOR并诱导自噬。在伤口愈合方面，Gadd34 KO MEF(小鼠胚胎成纤维细胞)的伤口愈合速度快于野生型MEF。与Gadd34KO小鼠相比，WT小鼠在迁移的巨噬细胞和肌成纤维细胞中表达更多的肌球蛋白IIA。这些结果表明，Gadd34通过肌球蛋白IIA的表达负性调节伤口愈合过程中的细胞迁移。

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.