miR-22-3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis
miR-22-3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis
复制标题
miR-22-3p通过CBL/p-EGFR/p-STAT3/GAP43/p-GAP43轴增强初级感觉神经元的内在再生能力
DOI：
10.1002/jcp.29338
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发表时间：
2019-10-29
影响因子：
5.6
通讯作者：
Feng, Shiqing
中科院分区：
文献类型：
--
作者：
Li, Bo;Wang, Zhijie;Feng, Shiqing
脊髓损伤(SCI)是一种破坏性疾病。加强内在再生能力的策略对于脊髓损伤的恢复从根本上预防感觉障碍的发生非常重要。表皮生长因子(EGF)对初级感觉神经元突起的生长作用有限，这是由于磷酸化的表皮生长因子受体(p-EGFR)的降解依赖于Casitas B系淋巴瘤(CBL)(一种E3泛素蛋白连接酶)。4个数据库预测的MIR-22-3p可能通过STAT3/GAP43途径而不是ERK1/2轴靶向CBL抑制CBL的表达，增加p-EGFR水平和突起长度。损伤后EGF、EGFR和miR-22-3p表达显著下调。体内应用miR-22-3p Agomir可调节CBL/p-EGFR/p-STAT3/GAP43/p-GAP43轴，恢复脊髓感觉传导功能。本研究阐明了EGF对成人初级感觉神经元突起的促进作用有限的机制，靶向miR-22-3p可能成为治疗脊髓损伤后感觉功能障碍的新策略。
Spinal cord injury (SCI) is a devastating disease. Strategies that enhance the intrinsic regenerative ability are very important for the recovery of SCI to radically prevent the occurrence of sensory disorders. Epidermal growth factor (EGF) showed a limited effect on the growth of primary sensory neuron neurites due to the degradation of phosphorylated-epidermal growth factor receptor (p-EGFR) in a manner dependent on Casitas B-lineage lymphoma (CBL) (an E3 ubiquitin-protein ligase). MiR-22-3p predicted from four databases could target CBL to inhibit the expression of CBL, increase p-EGFR levels and neurites length via STAT3/GAP43 pathway rather than Erk1/2 axis. EGF, EGFR, and miR-22-3p were downregulated sharply after injury. In vivo miR-22-3p Agomir application could regulate CBL/p-EGFR/p-STAT3/GAP43/p-GAP43 axis, and restore spinal cord sensory conductive function. This study clarified the mechanism of the limited promotion effect of EGF on adult primary sensory neuron neurite and targeting miR-22-3p could be a novel strategy to treat sensory dysfunction after SCI.