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Updated: Oct 13, 2026

Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy
Published on: September 27, 2024
A neutrophil-epithelial thrombospondin‑1-CD36-c‑Jun N‑terminal kinase axis orchestrates mucosal barrier failure in
Yiwen Wang1,2, Ran Li2, Mengmeng Zhuang1,2
1Department of Burn Surgery, The Affiliated Huaihai Hospital of Xuzhou Medical University, 226 Tongshan Street, Yunlong District, Xuzhou, Jiangsu Province 221004, China.
Background:
Intestinal barrier failure following ischemia-reperfusion (IR) injury is a critical event that drives lethal systemic complications; however, the specific intercellular signals governing epithelial cell fate under these pathological conditions remain incompletely understood.
Methods:
We performed single-cell ribonucleic acid sequencing (scRNA-seq) on intestinal tissues from a murine IR model to map intercellular communication networks. The identified ligand-receptor pair was functionally validated using neutrophil-specific thrombospondin-1 (Thbs1) knockout mice, combined with pharmacological inhibition and activation of CD36, as well as biochemical and histological analyses.
Results:
scRNA-seq analysis of the IR-injured gut revealed a key neutrophil-epithelial signaling pathway mediated by the Thbs1-Cd36 ligand-receptor pair. Neutrophil-specific genetic ablation of Thbs1 markedly attenuated IR-induced epithelial apoptosis and barrier disruption. Mechanistically, THBS1 binding to epithelial CD36 activated JNK signaling, mediating a proapoptotic cascade. CD36 inhibition was protective, whereas its activation bypassed the requirement for THBS1 and provoked mucosal injury.
Conclusions:
Our study elucidates a key mechanism of gut barrier failure and identifies the THBS1-CD36-JNK axis as a promising therapeutic target for mitigating intestinal IR injury in critical conditions such as burns and shock.
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