miR-27a-3p 通过 Wnt/β-catenin 信号调节肠细胞的增殖和分化。

IF 5.9 1区 生物学 Q2 CELL BIOLOGY Cell Proliferation Pub Date : 2024-09-27 DOI:10.1111/cpr.13757
Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L Weiss, Qingding Wang, B Mark Evers
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引用次数: 0

摘要

肠干细胞分化为吸收性肠细胞,其特点是刷状缘酶增加,如肠碱性磷酸酶(IAP),占绒毛终末分化细胞的大多数(95%)。肠上皮细胞完整性的丧失在炎症性疾病和胃肠道感染中起着关键作用。在这里,我们发现肠道微RNA(miR)-27a-3p是肠上皮细胞增殖和肠细胞分化的重要调节因子。抑制内源性 miR-27a-3p 会导致小鼠和人类小肠器官组织中肠细胞分化增加和肠上皮细胞增殖减少。从机理上讲,miR-27a-3p 至少部分是通过调节视黄酸受体α(RXRα)来调节肠细胞的分化和增殖的,视黄酸受体α是 Wnt/β-catenin 信号的调节器。抑制 miR-27a-3p 会增加 RXRα 的表达,同时降低活性 β-catenin 和细胞周期蛋白 D1 的表达。相反,过量表达 miR-27a-3p mimic 会降低 RXRα 的表达,增加活性 β-catenin 和细胞周期蛋白 D1 的表达。此外,过量表达 miR-27a-3p 模拟物会导致肠细胞分化受损和肠上皮细胞增殖增加。抑制 Wnt 可减轻或阻止这些变化。我们的研究表明,miR-27a-3p/RXRα/Wnt/β-catenin 通路对维持小肠肠细胞稳态非常重要。
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miR-27a-3p regulates intestinal cell proliferation and differentiation through Wnt/β-catenin signalling.

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at least in part through the regulation of retinoic acid receptor α (RXRα), a modulator of Wnt/β-catenin signalling. Repression of miR-27a-3p increases the expression of RXRα and concomitantly, decreases the expression of active β-catenin and cyclin D1. In contrast, overexpression of miR-27a-3p mimic decreases the expression of RXRα and increases the expression of active β-catenin and cyclin D1. Moreover, overexpression of the miR-27a-3p mimic results in impaired enterocyte differentiation and increases intestinal epithelial cell proliferation. These alterations were attenuated or blocked by Wnt inhibition. Our study demonstrates an miR-27a-3p/RXRα/Wnt/β-catenin pathway that is important for the maintenance of enterocyte homeostasis in the small intestine.

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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
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