Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.
Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine.
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转录因子HNF4在肠道中的多重作用和调控机制。
DOI：
10.3389/fendo.2023.1232569
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
肝细胞核因子4-α（HNF 4 α）驱动着一系列复杂的跨多个器官的转录程序。除了先前在肝脏中的功能外，HNF 4 α在肾脏，肠道和胰腺中具有关键作用。在肠中，HNF 4及其辅助转录因子具有多种功能，包括但不限于肠成熟、分化、再生和干细胞更新。HNF 4 α和它的丝氨酸限制性辅基HNF 4 γ之间的功能冗余，以及与其他转录因子的共调节驱动这些功能。HNF 4的表达失调导致广泛的疾病表现，包括肠道中慢性炎症状态的发展。本文就HNF 4在肠道中的多种分子机制及其翻译途径进行综述。我们的目的是通过HNF 4转录因子的透镜来介绍理解肠道遗传学和胃肠道疾病复杂性的新观点。
Hepatocyte nuclear factor 4-alpha (HNF4α) drives a complex array of transcriptional programs across multiple organs. Beyond its previously documented function in the liver, HNF4α has crucial roles in the kidney, intestine, and pancreas. In the intestine, a multitude of functions have been attributed to HNF4 and its accessory transcription factors, including but not limited to, intestinal maturation, differentiation, regeneration, and stem cell renewal. Functional redundancy between HNF4α and its intestine-restricted paralog HNF4γ, and co-regulation with other transcription factors drive these functions. Dysregulated expression of HNF4 results in a wide range of disease manifestations, including the development of a chronic inflammatory state in the intestine. In this review, we focus on the multiple molecular mechanisms of HNF4 in the intestine and explore translational opportunities. We aim to introduce new perspectives in understanding intestinal genetics and the complexity of gastrointestinal disorders through the lens of HNF4 transcription factors.
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