Sun Junjie, Ji Yuhua, Liang Qingyun, Ming Mengru, Chen Yuhan, Zhang Qi, Zhou Songlin, Shen Mi, Ding Fei
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Front Mol Neurosci. 2022 May 17;15:888523. doi: 10.3389/fnmol.2022.888523. eCollection 2022.
Protein acetylation, regulated by acetyltransferases and deacetylases, is an important post-translational modification that is involved in numerous physiological and pathological changes in peripheral nerves. There is still no systematical analysis on the expression changes of protein acetylation regulators during sciatic nerve development, injury, and regeneration. Here, we sequenced and analyzed the transcriptome of mouse sciatic nerves during development and after injury. We found that the changes in the expression of most regulators followed the rule that "development is consistent with regeneration and opposite to injury." Immunoblotting with pan-acetylated antibodies also revealed that development and regeneration are a process of increased acetylation, while injury is a process of decreased acetylation. Moreover, we used bioinformatics methods to analyze the possible downstream molecules of two key regulators, histone deacetylase 1 (Hdac1) and lysine acetyltransferase 2b (Kat2b), and found that they were associated with many genes that regulate the cell cycle. Our findings provide an insight into the association of sciatic nerve development, injury, and regeneration from the perspective of protein acetylation.
蛋白质乙酰化受乙酰转移酶和脱乙酰酶调控,是一种重要的翻译后修饰,参与外周神经的众多生理和病理变化。目前尚无关于坐骨神经发育、损伤和再生过程中蛋白质乙酰化调节因子表达变化的系统分析。在此,我们对小鼠坐骨神经发育过程中和损伤后的转录组进行了测序和分析。我们发现,大多数调节因子的表达变化遵循“发育与再生一致,与损伤相反”的规律。用泛乙酰化抗体进行免疫印迹分析也表明,发育和再生是乙酰化增加的过程,而损伤是乙酰化减少的过程。此外,我们使用生物信息学方法分析了两个关键调节因子组蛋白脱乙酰酶1(Hdac1)和赖氨酸乙酰转移酶2b(Kat2b)可能的下游分子,发现它们与许多调节细胞周期的基因相关。我们的研究结果从蛋白质乙酰化的角度为坐骨神经发育、损伤和再生之间的关联提供了见解。