Cross-talk between KLF4 and STAT3 regulates axon regeneration.
Cross-talk between KLF4 and STAT3 regulates axon regeneration.
复制标题
DOI：
10.1038/ncomms3633
复制
发表时间：
2013
影响因子：
16.6
通讯作者：
Zhang CL
中科院分区：
文献类型：
--
作者：
Qin S;Zou Y;Zhang CL
细胞因子诱导的信号转导子和转录激活子3（STAT 3）的激活促进成年中枢神经系统（CNS）中受损轴突的再生。在这里，我们表明，KLF 4物理相互作用与STAT 3后，酪氨酸705（Y 705）的磷酸化酪氨酸磷酸化的STAT 3。这种相互作用通过阻断STAT 3的DNA结合活性来抑制STAT 3依赖性基因的表达。体内KLF 4的缺失通过Janus激酶（JAK）-STAT 3信号转导诱导成年视网膜神经节细胞（RGC）的轴突再生。这种再生可以通过外源性细胞因子处理或去除称为细胞因子信号传导抑制因子3（SOCS 3）的内源性JAK-STAT 3途径抑制剂来大大增强。这些发现揭示了KLF 4和活化的STAT 3在轴突再生调节中的意想不到的串扰，这可能在促进损伤的成年CNS的修复中具有治疗意义。
Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signaling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signaling 3 (SOCS3). These findings reveal an unexpected crosstalk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.