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

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-05-09 DOI:10.1038/s41420-025-02511-y

Yao Liu, Lanqing Wu, Xiaoli Li, Yongyu Chen, Ruidong Chen, Caiyun Lv, Juan Chen, Xinjuan Fan, Guangxin Duan, Fan Zhong, Qi Sun, Qianyun Shi, Hengli Ni, Lina Sun, Jiaying Xu, Wen Tang, Jianming Li

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Abstract

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.

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PYY对炎症性肠病SATB2缺乏引起的肠黏膜缺损的保护作用

结肠粘膜修复受损是炎症性肠病（IBD）的一个关键问题。SATB2对于维持结肠上皮稳态至关重要，但其在粘膜修复中的作用尚不清楚。在这项研究中，流式细胞术用于评估SATB2在辐射损伤模型中结肠上皮修复中的作用。SATB2基因敲除小鼠表现出上皮修复缺陷，杯状细胞和肠内分泌细胞明显减少。在机制上，SATB2直接调控PPAR-γ的转录，PYY被观察到易位到细胞核中并促进PPAR-γ靶基因的转录。在来自克罗恩病患者的类器官中，补充PYY可显著改善上皮再生，优于PPAR-γ激动剂罗格列酮。综上所述，SATB2缺乏会损害结肠上皮的修复，而PYY可以通过激活PPAR-γ依赖的转录来挽救结肠上皮的修复。这些发现表明PYY可能作为一种有希望的治疗分子来促进IBD的上皮修复。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.