Zhou Yun, Chi Shuiqing, Li Shuai, Luo Zhibin, Rong Liying, Zhang Mengxin, Chen Yunshang, Guo Jialing, Yang Dehua, Zhang Xi, Cao Guoqing, Tang Shao-Tao
Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, China.
Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Cell Proteomics. 2025 Jul 11;24(8):101032. doi: 10.1016/j.mcpro.2025.101032.
Hirschsprung disease (HSCR) is a common peripheral neurodevelopmental disorder and impaired enteric neural crest cell 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 enteric neural crest cell migration. Here, we revealed a significant downregulation of SCGN by protein profiles using tandem mass tag 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 (lymphoid enhancer-binding factor 1 [LEF-1]), which directly activated the transcription of the cell adhesion molecule (neural cell adhesion molecule 1 [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 lymphoid enhancer-binding factor 1/neural cell adhesion molecule 1 axis. The findings could contribute to the diagnostic and therapeutic strategies for HSCR.
先天性巨结肠症（HSCR）是一种常见的周围神经发育障碍，而肠神经嵴细胞迁移受损是关键因素之一。分泌粒蛋白（SCGN）已被证明在中枢神经再生过程中的吻侧迁移流中起关键作用。然而，关于SCGN在肠神经嵴细胞迁移中的作用，人们知之甚少。在这里，我们通过串联质谱标签蛋白质谱揭示了HSCR病变结肠组织中SCGN的显著下调。我们发现SCGN表达降低会在体外和体内阻碍细胞迁移。从机制上讲，SCGN上调转录因子（淋巴样增强子结合因子1 [LEF-1]），后者直接激活细胞粘附分子（神经细胞粘附分子1 [NCAM1]）的转录，从而促进细胞迁移。总之，本研究通过证明SCGN通过淋巴样增强子结合因子1/神经细胞粘附分子1轴参与影响神经嵴细胞迁移，阐明了SCGN在HSCR发病机制中的作用。这些发现可能有助于HSCR的诊断和治疗策略。
