Integrative analysis links ferroptosis to necrotizing enterocolitis and reveals the role of ACSL4 in immune disorders

Dan Dang; Chuan Zhang; Zhaoli Meng; Xiaoming Lv; Zhenyu Li; Jiaqi Wei; Hui Wu

doi:10.1016/j.isci.2022.105406

Integrative analysis links ferroptosis to necrotizing enterocolitis and reveals the role of ACSL4 in immune disorders

iScience. 2022 Oct 19;25(11):105406. doi: 10.1016/j.isci.2022.105406. eCollection 2022 Nov 18.

Authors

Dan Dang¹, Chuan Zhang², Zhaoli Meng³, Xiaoming Lv¹, Zhenyu Li¹, Jiaqi Wei¹, Hui Wu¹

Affiliations

¹ Department of Neonatology, First Hospital of Jilin University, Changchun 130021, China.
² Department of Pediatric Surgery, First Hospital of Jilin University, Changchun 130021, China.
³ Department of Translational Medicine Research Institute, First Hospital of Jilin University, Changchun 130021, China.

Abstract

Multiple types of regulated cell death (RCD) have been demonstrated to cause gut barrier dysfunction in necrotizing enterocolitis (NEC); however, whether and how ferroptosis is involved in NEC remains unknown. Here, ferroptosis was identified to play a role in NEC using bioinformatics analyses and wet experiments. Inhibition of ferroptosis significantly alleviated NEC in newborn mice. ACSL4 expression levels were augmented and positively correlated with ferroptosis in NEC. Surprisingly, ACSL4 was critically correlated with multiple types of RCD, including autophagy, apoptosis and pyroptosis, as well as hypoxia and inflammation. Besides, ACSL4 was positively correlated with the abundance of multiple types of immune cells, including macrophage, activated dendritic cell, neutrophil and regulatory T cell. Conclusively, we first identified the involvement and role of ferroptosis in NEC and revealed the potential effects of ACSL4 on immune disorders, which could provide a rationale for future research on ferroptosis in NEC.

Keywords: Biological sciences; Immunology; Molecular biology.