Zhang Siqin, Wang Zhihao, Zhang Yuyan, Dong Xiaowu, Zhu Qingtian, Yuan Chenchen, Lu Guotao, Gong Weijuan, Bi Yawei, Wang Yaodong
Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Yangzhou University, Kunshan, Suzhou, Jiangsu, China; Department of Gastroenterology, Pancreatic Center, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Department of Gastroenterology, Pancreatic Center, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Biochem Biophys Res Commun. 2025 Jan;744:151134. doi: 10.1016/j.bbrc.2024.151134. Epub 2024 Dec 13.
Neutrophil extracellular traps (NETs) play a significant role in the development of acute pancreatitis (AP). The actin-binding protein LASP1 regulates proteins associated with the cytoskeleton, yet its precise involvement in NETs and AP remains to be elucidated.
To investigate the role of LASP1 in NETs and AP, several bioinformatics methods, such as weighted gene co-expression network analysis (WGCNA), differential analysis, and least absolute shrinkage and selection operator (LASSO) regression, were utilized to screen for feature genes based on the Gene Expression Omnibus (GEO) dataset. To further assess the impact of LASP1, both an in vitro model of 12-myristic-13-acetate phobolol (PMA)-induced NETs and a caerulein-induced AP model were employed.
Through WGCNA, AP-related module genes were screened, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted to identify enriched pathways and functions. Six characteristic genes were identified through LASSO regression screening, with LASP1 being the most distinct. LASP1 reduces the generation of NETs induced by PMA in vitro. Mechanistically, LASP1 may increase F-actin protein levels by inhibiting the depolymerization of F-actin. Furthermore, our study utilizing a mouse AP model demonstrated that the LSAP1 recombinant protein effectively alleviated pancreatic necrosis in mice afflicted with AP.
LASP1 inhibits the formation of NETs and may alleviate AP by increasing the level of F-actin protein.
中性粒细胞胞外陷阱（NETs）在急性胰腺炎（AP）的发生发展中起重要作用。肌动蛋白结合蛋白LASP1调节与细胞骨架相关的蛋白质，但其在NETs和AP中的具体作用仍有待阐明。
为了研究LASP1在NETs和AP中的作用，利用了几种生物信息学方法，如加权基因共表达网络分析（WGCNA）、差异分析和最小绝对收缩和选择算子（LASSO）回归，基于基因表达综合数据库（GEO）数据集筛选特征基因。为了进一步评估LASP1的影响，采用了12-肉豆蔻酸-13-乙酸佛波醇（PMA）诱导的NETs体外模型和雨蛙肽诱导的AP模型。
通过WGCNA筛选出与AP相关的模块基因，进行京都基因与基因组百科全书（KEGG）和基因本体论（GO）富集分析以确定富集的途径和功能。通过LASSO回归筛选鉴定出6个特征基因，其中LASP1最为显著。LASP1在体外可减少PMA诱导的NETs的产生。机制上，LASP1可能通过抑制F-肌动蛋白的解聚来增加F-肌动蛋白的蛋白水平。此外，我们利用小鼠AP模型的研究表明，LSAP1重组蛋白可有效减轻患AP小鼠的胰腺坏死。
LASP1抑制NETs的形成，并可能通过增加F-肌动蛋白蛋白水平来减轻AP。
