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Related Experiment Video

Updated: Feb 4, 2026

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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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
|February 2, 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 increasing IEC death and gut barrier dysfunction.

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 critical in sepsis pathogenesis.
  • The molecular mechanisms protecting intestinal epithelial cells (IECs) from sepsis-induced apoptosis 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 regulates IEC apoptosis during sepsis.

Main Methods:

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

Main Results:

  • Gab1 expression was reduced in the intestines of septic individuals and models.
  • Epithelial Gab1 deficiency exacerbated LPS-induced sepsis, increasing IEC apoptosis and mortality.
  • Gab1 protected IECs by activating NF-κB via IKKβ, downregulating apoptotic gene expression in response to TNF-α.

Conclusions:

  • Gab1 plays a crucial protective role in sepsis-induced intestinal injury by maintaining apoptotic balance.
  • Gab1 is essential for intestinal homeostasis during sepsis.
  • Targeting Gab1 may offer therapeutic strategies for sepsis management, focusing on immune homeostasis and barrier function restoration.