Epithelial Gab1 Restricts Sepsis‐Induced Intestinal Injury by Orchestrating TNF/NF‐κB Axis
Wei Jin, Yanchuang Wu, Xiaoqing Cheng, Yu Pan, Lifeng He, Yun Xu, Jiaqi Xu, Xue Zhang
TL;DR
Gab1 protects intestinal cells from dying during sepsis by controlling inflammation and maintaining gut barrier function.
Contribution
Gab1's protective role in sepsis is revealed through its regulation of apoptosis and NF-κB signaling in intestinal epithelial cells.
Findings
Gab1 deficiency in intestinal epithelial cells increases susceptibility to sepsis and apoptosis.
Gab1 activates NF-κB to regulate apoptotic genes and sustain intestinal homeostasis.
Restoring Gab1 may offer therapeutic strategies for sepsis management.
Abstract
A series of intestine‐related alterations have been considered a key factor in triggering sepsis, with increased apoptosis of intestinal epithelial cells (IECs) notably contributing to this process. Compromised gut barrier due to IEC apoptosis promotes bacterial translocation and inflammatory responses, which in turn escalates to further IEC death and barrier defects. Nevertheless, the precise mechanisms that safeguard IECs from apoptosis and interrupt this vicious cycle are yet to be elucidated. Here, we report that Grb2‐associated binder 1 (Gab1) expression is diminished in the intestines of both septic patients and established sepsis models. Epithelial Gab1 deficiency rendered mice susceptible to lipopolysaccharide (LPS)‐induced sepsis by sensitizing IECs to apoptosis, thereby contributing to systemic inflammation and markedly exacerbating septic lethality. Mechanistically, Gab1…
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Taxonomy
TopicsNF-κB Signaling Pathways · Immune Response and Inflammation · Protein Tyrosine Phosphatases