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Epithelial Gab1 Restricts Sepsis-Induced Intestinal Injury by Orchestrating TNF/NF-κB Axis.

Wei Jin1, Yanchuang Wu2, Xiaoqing Cheng2

  • 1Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China, zju.edu.cn.

Mediators of Inflammation
|March 25, 2026
PubMed
Summary
This summary is machine-generated.

Grb2-associated binder 1 (Gab1) protects intestinal epithelial cells (IECs) from apoptosis during sepsis. Gab1 deficiency worsens sepsis outcomes by impairing gut barrier function and increasing inflammation.

Keywords:
adaptor protein Gab1apoptosisintestinal epithelial cellsintestinal injurysepsis

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Area of Science:

  • Cell Biology
  • Immunology
  • Gastroenterology

Background:

  • Intestinal barrier dysfunction and epithelial cell apoptosis are key contributors to sepsis pathogenesis.
  • The precise mechanisms protecting intestinal epithelial cells (IECs) from apoptosis during sepsis remain unclear.

Purpose of the Study:

  • To investigate the role of Grb2-associated binder 1 (Gab1) in sepsis-induced intestinal injury.
  • To elucidate the mechanisms by which Gab1 influences IEC apoptosis and sepsis outcomes.

Main Methods:

  • Examined Gab1 expression in septic patients and sepsis models.
  • Utilized epithelial Gab1-deficient mice to assess susceptibility to lipopolysaccharide (LPS)-induced sepsis.
  • Investigated the molecular pathways involving Gab1, IKKβ, NF-κB, and TNF-α signaling in IEC apoptosis.

Main Results:

  • Gab1 expression was reduced in the intestines of septic individuals and models.
  • Epithelial Gab1 deficiency sensitized mice to LPS-induced sepsis, increasing IEC apoptosis, systemic inflammation, and mortality.
  • Gab1 suppressed TNF-α-induced apoptosis by activating IKKβ-dependent NF-κB signaling and regulating apoptotic gene expression.

Conclusions:

  • Gab1 plays a protective role in sepsis-related intestinal injury by maintaining apoptotic balance and intestinal homeostasis.
  • Gab1 represents a potential therapeutic target for sepsis management, particularly for restoring immune balance and barrier integrity.