Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo 315211, China.
Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, Medical School of Ningbo University, Ningbo 315211, China.
J Diabetes Res. 2017;2017:8103904. doi: 10.1155/2017/8103904. Epub 2017 Aug 16.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the "neurotrophin-MAPK signaling pathway" was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.
糖尿病周围神经病变（DPN）是糖尿病（DM）的常见并发症。由于其发病机制仍存在争议，大多数患者未得到正确诊断或治疗。在这项研究中，人类全基因组微阵列分别鉴定出 DM 患者和 DPN 患者中的 2898 个和 4493 个差异表达基因（DEGs）。进一步的 KEGG 通路分析表明，DPN 和 DM 共有四个通路，包括细胞凋亡、B 细胞受体信号通路、内吞作用和 Toll 样受体信号通路。通过比较 DPN 和 DM 鉴定出的 DEGs 在 MAPK 信号通路、NOD 样受体信号通路和神经营养因子信号通路中显著富集，而“神经营养因子-MAPK 信号通路”显著下调。神经生长因子-MAPK 信号通路中的 7 个 DEG 在另外 78 个样本中进行了验证，结果证实了初始微阵列的发现。这些发现表明，神经营养因子-MAPK 信号通路的下调可能是 DPN 发病机制的主要机制，从而为 DPN 的治疗提供了一种潜在的方法。
