SLC26A3 (DRA, the Congenital Chloride Diarrhea Gene): A Novel Therapeutic Target for Diarrheal Diseases.

IF 7.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Cellular and Molecular Gastroenterology and Hepatology Pub Date : 2024-12-28 DOI:10.1016/j.jcmgh.2024.101452

Anoop Kumar, Dulari Jayawardena, Shubha Priyamvada, Arivarasu N Anbazhagan, Ishita Chatterjee, Seema Saksena, Pradeep K Dudeja

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SLC26A3（DRA，先天性氯化腹泻基因）：腹泻病的新治疗靶点。

与肠道感染、肠道炎症和遗传缺陷相关的腹泻是主要的健康负担，并导致显著的发病率和死亡率。肠道中液体和电解质的吸收和/或分泌受损是腹泻的标志。哺乳动物胃肠道中的电中性NaCl吸收涉及Na+/H+和Cl-/HCO3-交换剂的偶联。SLC26A3 （Down Regulated in Adenoma， DRA）是参与腔内Cl-吸收和HCO3-分泌的主要阴离子交换剂。SLC26A3基因的突变导致一种称为先天性氯化物腹泻（CLD）的严重疾病。多项研究表明，在EPEC、C. rodentium、沙门氏菌、clostridiides difficile和Cryptosporidium parum感染引起的感染性腹泻疾病中，DRA功能和/或表达下调。此外，在IBD患者和IBD小鼠模型（如DSS、TNBS、过继性t细胞转移、抗cd -40和IL-10 KO结肠炎）的结肠黏膜中，DRA水平严重降低。此外，表现为腹泻的遗传缺陷包括微绒毛夹杂病（MVID）、角蛋白8缺失、CDX-2和HNF1α/1β等转录因子敲除小鼠模型也表现出DRA的严重下调。此外，最近的研究表明，DRA不仅对氯化物吸收至关重要，而且在维持肠道上皮屏障完整性和微生物组组成方面也起着关键作用，现在已成为IBD的易感基因。在这篇综述中，我们提供了强有力的证据，证明DRA可能作为一种新的治疗靶点，不仅可以纠正腹泻表型，还可以改善病原体感染或IBD的肠道屏障完整性和炎症。

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

Cellular and Molecular Gastroenterology and Hepatology Medicine-Gastroenterology

CiteScore

13.00

自引率

2.80%

发文量

246

审稿时长

42 days

期刊介绍： "Cell and Molecular Gastroenterology and Hepatology (CMGH)" is a journal dedicated to advancing the understanding of digestive biology through impactful research that spans the spectrum of normal gastrointestinal, hepatic, and pancreatic functions, as well as their pathologies. The journal's mission is to publish high-quality, hypothesis-driven studies that offer mechanistic novelty and are methodologically robust, covering a wide range of themes in gastroenterology, hepatology, and pancreatology. CMGH reports on the latest scientific advances in cell biology, immunology, physiology, microbiology, genetics, and neurobiology related to gastrointestinal, hepatobiliary, and pancreatic health and disease. The research published in CMGH is designed to address significant questions in the field, utilizing a variety of experimental approaches, including in vitro models, patient-derived tissues or cells, and animal models. This multifaceted approach enables the journal to contribute to both fundamental discoveries and their translation into clinical applications, ultimately aiming to improve patient care and treatment outcomes in digestive health.