分泌素下调通过抑制LEF-1/NCAM1轴损害巨结肠疾病中的神经细胞迁移

IF 6.1 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Molecular & Cellular Proteomics Pub Date : 2025-07-11 DOI:10.1016/j.mcpro.2025.101032

Yun Zhou, Shuiqing Chi, Shuai Li, Zhibin Luo, Liying Rong, Mengxin Zhang, Yunshang Chen, Jialing Guo, Dehua Yang, Xi Zhang, Guoqing Cao, Shao-Tao Tang

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引用次数: 0

摘要

巨结肠病（Hirschsprung disease， HSCR）是一种常见的周围神经发育障碍，而肠道神经嵴细胞（enteric neural crest cell， ENCC）迁移障碍是其关键因素之一。分泌素（SCGN）已被证明在中枢神经再生的吻侧迁移流中起关键作用。然而，关于SCGN在ENCC迁移中的作用的知识缺乏。在这里，我们通过串联质量标签（TMT）的蛋白谱揭示了HSCR病变结肠组织中SCGN的显著下调。我们发现SCGN的表达降低会阻碍细胞在体内和体外的迁移。机制上，SCGN上调转录因子LEF-1，直接激活细胞粘附分子NCAM1的转录，从而促进细胞迁移。总之，本研究通过证明SCGN通过LEF-1/NCAM1轴影响神经嵴细胞迁移，阐明了SCGN在HSCR发病中的作用。研究结果可能有助于HSCR的诊断和治疗策略。

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Secretagogin Downregulation Impairs Nerve Cell Migration in Hirschsprung Disease via Inhibition of the LEF-1/NCAM1 Axis.

Hirschsprung disease (HSCR) is a common peripheral neurodevelopmental disorder, and impaired enteric neural crest cell (ENCC) migration is one of the key factors. Secretagogin (SCGN) has been demonstrated to play a critical role in the rostral migratory stream during central nerve regeneration. However, there is a paucity of knowledge on the role of SCGN in ENCC migration. Here we revealed a significant downregulation of SCGN by protein profiles using tandem mass tag (TMT) in HSCR lesion colon tissues. We identified decreased expression of SCGN could hinder cell migration in vitro and in vivo. Mechanistically, SCGN upregulated the transcription factor LEF-1, which directly activated the transcription of the cell adhesion molecule NCAM1, thereby promoting cell migration. In conclusion, this study elucidates the role of SCGN in HSCR pathogenesis by demonstrating its involvement in affecting neural crest cell migration through the LEF-1/NCAM1 axis. The findings could contribute to the diagnostic and therapeutic strategies for HSCR.

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来源期刊

Molecular & Cellular Proteomics 生物-生化研究方法

CiteScore

11.50

自引率

4.30%

发文量

131

审稿时长

84 days

期刊介绍： The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes