Peptide Derived from AHNAK Inhibits Cell Migration and Proliferation in Hirschsprung’s Disease by Targeting the ERK1/2 Pathway
| Autor: | Weibing Tang, Zhonghong Wei, Hongxing Li, Zhengke Zhi, Huan Chen, Yuhan Li, Lingling Zhou, Binyu Wang, Xiurui Lv |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAP Kinase Signaling System Endogeny Biochemistry Pathogenesis 03 medical and health sciences Downregulation and upregulation Cell Movement Laminin medicine Humans Hirschsprung Disease Gene Hirschsprung's disease Cell Proliferation 030102 biochemistry & molecular biology biology Membrane Proteins Neural crest Cell migration General Chemistry medicine.disease Neoplasm Proteins Cell biology 030104 developmental biology biology.protein Peptides |
| Zdroj: | Journal of Proteome Research. 20:2308-2318 |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.0c00811 |
| Popis: | Hirschsprung's disease (HSCR) is characterized by the lack of ganglion cells in the distal part of the digestive tract. It occurs due to migration disorders of enteric neural crest cells (ENCCs) from 5 to 12 weeks of embryonic development. More and more studies show that HSCR is a result of the interaction of multiple genes and the microenvironments, but its specific pathogenesis has not been fully elucidated. Studies have confirmed that many substances in the intestinal microenvironment, such as laminin and β1-integrin, play a vital regulatory role in cell growth and disease progression. In addition to these high-molecular-weight proteins, research on endogenous polypeptides derived from these proteins has been increasing in recent years. However, it is unclear whether these endogenous peptides have effects on the migration of ENCCs and thus participate in the occurrence of HSCR. Previously, our research group found that compared with the normal intestinal tissue, the expression of AHNAK protein in the stenosed intestinal tissue of HSCR patients was significantly upregulated, and overexpression of AHNAK could inhibit cell migration and proliferation. In this study, endogenous peptides were extracted from the normal control intestinal tissue and the stenosed HSCR intestinal tissue. The endogenous polypeptide expression profile was analyzed by liquid chromatography-mass spectrometry, and multiple peptides derived from AHNAK protein were found. We selected one of them, "EGPEVDVNLPK", for research. Because there is no uniform naming system, this peptide is temporarily named PDAHNAK (peptide derived from AHNAK). This project aims to clarify the potential role of PDAHNAK in the development of HSCR and to further understand its relationship with its precursor protein AHNAK and how they contribute to the development of HSCR. |
| Databáze: | OpenAIRE |
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