P0116 The Protective Role of PYY in Intestinal Mucosal Defects Induced by SATB2 Deficiency in Inflammatory Bowel Disease
Authors: Liu Y , Wu L , Li X , Chen R , Sun Q , Tang W 
Published: January 2025

Abstract

Background
To investigate the mechanisms by which SATB2 deficiency leads to impaired intestinal mucosal repair in inflammatory bowel disease, and to evaluate the therapeutic potential of peptide YY (PYY) in ameliorating intrinsic defects of the epithelium.

Methods
Flow cytometry was used to detect the correlation between SATB2 and colonic epithelial repair in a radiation-induced injury model. Colonic mucosal repair impairment was validated in SATB2 knockout mice. The impact of SATB2 loss on enteroendocrine hormones, particularly PYY, and its influence on repair were assessed in vivo and ex vivo. The regulatory mechanism of SATB2 on PPAR-γ and the molecular mechanisms underlying PYY were explored using confocal microscopy, nuclear-cytoplasmic fractionation, immunoblotting, and luciferase reporter assays. PYY’s effects on intestinal epithelial repair were observed in organoids from Crohn’s disease patients.

Results
The expression of Satb2 correlated with the extent of colonic mucosal repair following injury. Loss of Satb2 significantly restricted colonic epithelial repair, resulting in widespread loss of secretory lineage cells such as goblet and enteroendocrine cells. The most prominent enteroendocrine hormone, PYY, showed a significant decrease in colonic mucosa after Satb2 loss. At the molecular level, Satb2 directly regulated the transcription of PPAR-γ. PYY could enter the nucleus and promote the transcription of downstream genes of PPAR-γ. At the organoid level, the reparative ability of PYY in promoting intestinal epithelial repair was superior to the PPAR-γ agonist rosiglitazone. Additionally, PYY was found to ameliorate intrinsic defects in the colonic epithelium of Crohn’s disease patients.

Conclusion
The impairment of colonic epithelial repair resulting from Satb2 loss could be ameliorated through PYY supplementation, which facilitates repair by activating the transcription of downstream genes associated with PPAR-γ.

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