LASP1 inhibits the formation of NETs and alleviates acute pancreatitis by stabilizing F-actin polymerization in neutrophils

Siqin Zhang; Zhihao Wang; Yuyan Zhang; Xiaowu Dong; Qingtian Zhu; Chenchen Yuan; Guotao Lu; Weijuan Gong; Yawei Bi; Yaodong Wang

doi:10.1016/j.bbrc.2024.151134

LASP1 inhibits the formation of NETs and alleviates acute pancreatitis by stabilizing F-actin polymerization in neutrophils

Biochem Biophys Res Commun. 2024 Dec 13:744:151134. doi: 10.1016/j.bbrc.2024.151134. Online ahead of print.

Authors

Siqin Zhang¹, Zhihao Wang², Yuyan Zhang², Xiaowu Dong², Qingtian Zhu², Chenchen Yuan², Guotao Lu², Weijuan Gong³, Yawei Bi⁴, Yaodong Wang⁵

Affiliations

¹ 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.
² Department of Gastroenterology, Pancreatic Center, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
³ Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
⁴ Department of Gastroenterology, Chinese PLA General Hospital First Medical Center, Beijing, China.
⁵ Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Yangzhou University, Kunshan, Suzhou, Jiangsu, China. Electronic address: 18606265567@yzu.edu.cn.

PMID: 39708397
DOI: 10.1016/j.bbrc.2024.151134

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: LASP1 inhibits the formation of NETs and may alleviate AP by increasing the level of F-actin protein.

Keywords: Acute pancreatitis; F-actin; LASP1; NETs.