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Rab11FIP1-deficient mice develop spontaneous inflammation and show increased susceptibility to colon damage.

Sudiksha Rathan-Kumar1,2, Joseph T Roland1,2, Michael Momoh1,2

  • 1Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.

American Journal of Physiology. Gastrointestinal and Liver Physiology
|July 12, 2022
PubMed
Summary

Rab11-FIP1 deficiency impairs intestinal mucosal integrity by disrupting vesicle trafficking and reducing goblet cells. This leads to increased susceptibility to injury and inflammation in knockout mice.

Keywords:
MUC13Rab11Rab11FIP1Rab14colon

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Area of Science:

  • Cell Biology
  • Gastroenterology
  • Molecular Biology

Background:

  • Rab11a GTPase and its interacting proteins (Rab11-FIPs) are crucial for vesicle trafficking and cell polarity in epithelial cells.
  • The specific role of Rab11-FIP1 in maintaining intestinal mucosal integrity and its gastrointestinal phenotype were previously unreported.

Purpose of the Study:

  • To investigate the role of Rab11-FIP1 in maintaining colonic mucosal integrity.
  • To characterize the gastrointestinal phenotype of Rab11FIP1 knockout mice.

Main Methods:

  • Generated global Rab11FIP1 knockout (KO) mice.
  • Analyzed colonic tissue pathology using immunostaining and RNA-sequencing.
  • Assessed intestinal injury in KO and control mice following dextran sodium sulfate (DSS) treatment.

Main Results:

  • Rab11FIP1 KO mice exhibited increased lymphoid patches, immune cell infiltration, and reduced TFF3-positive goblet cells.
  • Deletion of Rab11FIP1 led to abnormal vesicle accumulation and MUC13 internalization.
  • Rab11FIP1 KO mice showed exacerbated weight loss and mucosal damage after DSS treatment.

Conclusions:

  • Rab11-FIP1 is essential for maintaining colonic mucosal integrity and cytoprotection mechanisms.
  • Loss of Rab11-FIP1 disrupts vesicle trafficking, leading to goblet cell reduction and impaired barrier function.
  • Rab11FIP1 deficiency sensitizes the colon to inflammatory injury.