Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA.
Mol Cell Neurosci. 2013 Sep;56:272-82. doi: 10.1016/j.mcn.2013.06.005. Epub 2013 Jul 3.
The transcription factor STAT3 has been implicated in axon regeneration. Here we investigate a role for STAT3 in sympathetic nerve sprouting after myocardial infarction (MI) - a common injury in humans. We show that NGF stimulates serine phosphorylation (S727) of STAT3 in sympathetic neurons via ERK1/2, in contrast to cytokine phosphorylation of Y705. Maximal sympathetic axon regeneration in vitro requires phosphorylation of both S727 and Y705. Furthermore, cytokine signaling is necessary for NGF-induced sympathetic nerve sprouting in the heart after MI. Transfection studies in neurons lacking STAT3 suggest two independent pools of STAT3, phosphorylated on either S727 or Y705, that regulate sympathetic regeneration via both transcriptional and non-transcriptional means. Additional data identify STAT3-microtubule interactions that may complement the well-characterized role of STAT3 stimulating regeneration associated genes. These data show that STAT3 is critical for sympathetic axon regeneration in vitro and in vivo, and identify a novel non-transcriptional mode of action.
转录因子 STAT3 被认为与轴突再生有关。在这里，我们研究了 STAT3 在心肌梗死（MI）后交感神经发芽中的作用——这是人类常见的损伤。我们发现，NGF 通过 ERK1/2 刺激交感神经元中 STAT3 的丝氨酸磷酸化（S727），与细胞因子磷酸化 Y705 相反。体外最大的交感神经轴突再生需要 S727 和 Y705 的磷酸化。此外，细胞因子信号对于 MI 后心脏中 NGF 诱导的交感神经发芽是必要的。在缺乏 STAT3 的神经元中转染研究表明，STAT3 有两个独立的磷酸化池，分别在 S727 或 Y705 上磷酸化，通过转录和非转录途径调节交感神经再生。其他数据确定了 STAT3-微管相互作用，这可能补充了 STAT3 刺激与再生相关基因的作用。这些数据表明，STAT3 对于体外和体内的交感神经轴突再生至关重要，并确定了一种新的非转录作用模式。
