研究动态
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通过调节uc.173,黄连苷A促进肠黏膜的更新。

Licochalcone A promotes renewal of intestinal mucosa through modulating uc.173.

发表日期:2023 Aug 14
作者: Yajun Wang, Yanwu Li, Chunhui Song, Junyu Ke, Yanqiu Zheng, Gang Chen, Ning Li
来源: JOURNAL OF ETHNOPHARMACOLOGY

摘要:

根据传统中药理论,甘草可以养血脾,从而增强消化系统功能。甘草通常被用于复方处方治疗肠道炎症性疾病。犁甲酚A (Lico A) 是甘草中的一种特征性分子。T-UCR(从超保守区域转录)是一类与肠道上皮细胞再生相关的新型长链非编码RNA。本研究旨在调查Lico A对肠道上皮细胞再生的影响及与uc.173相关的机制。使用IE-6和Caco-2细胞评估Lico A对肠道上皮细胞凋亡、增殖和迁移的影响。使用肠道器官样体探究Lico A促进肠道器官样体发育的体外效应和机制。使用C57BL/6J小鼠(包括正常小鼠和uc.173缺陷小鼠)检测Lico A对肠道黏膜再生的体内效应。Lico A处理的肠道上皮细胞中三种与肠道黏膜再生相关的T-UCR的表达发生改变。Lico A通过uc.173/miR-195通路促进IEC的增殖和抑制凋亡。48小时禁食的小鼠Lico A处理促进了肠道器官样体的发育和肠道黏膜的再生。此外,Lico A的应用可以恢复uc.173缺陷的肠道器官样体的生长停滞和uc.173缺陷小鼠的肠道黏膜萎缩。本文结果表明,靶向T-UCRs可能是促进上皮再生的一种新型治疗方法,并通过促进肠道黏膜再生,Lico A可能成为维护肠道上皮完整性的新型治疗药物。版权所有 ©2023 Elsevier B.V. 发表。
Licorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal.This study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal.IE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa.The expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration.Results in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity.Copyright © 2023. Published by Elsevier B.V.