The protective role of PYY in intestinal mucosal defects induced by SATB2 deficiency in inflammatory bowel disease

作者：Yao Liu, Lei Wu, Xiao‐Li Li, Yongyu Chen, Ruidong Chen, Caiyun Lv, Juan Chen, Xinjuan Fan, Guangxin Duan, Zhong Fan, Qi Sun, Qianyun Shi, Hengli Ni, Lina Sun, Jiaying Xu, Wen Tang, Jianming Li · 发表于：Cell Death Discovery · 年份：2025 · DOI：10.1038/s41420-025-02511-y · 被引用次数：3 · 研究领域：Digestive system and related health、Epigenetics and DNA Methylation、Helicobacter pylori-related gastroenterology studies

Impaired colonic mucosal repair is a critical issue in inflammatory bowel diseases (IBD). SATB2 is essential for maintaining colonic epithelial homeostasis, but its role in mucosal repair is unclear. In this study, flow cytometry was used to assess SATB2's role in colonic epithelial repair in a radiation injury model. SATB2 knockout mice exhibited defective epithelial repair, with a marked reduction in goblet and enteroendocrine cells. Mechanistically, SATB2 directly regulated PPAR-γ transcription, and PYY was observed to translocate into the nucleus and promote the transcription of PPAR-γ target genes. In organoids derived from patients with Crohn's disease, PYY supplementation significantly improved epithelial regeneration, outperforming the PPAR-γ agonist rosiglitazone. In conclusion, SATB2 deficiency impairs colonic epithelial repair, which can be rescued by PYY through activation of PPAR-γ-dependent transcription. These findings suggest that PYY may serve as a promising therapeutic molecule to promote epithelial repair in IBD.