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利福昔明通过减弱长链非编码RNA-HIF1A-AS2/miR-153-3p/HIF-1α/血管生成素-2轴抑制小肠血管发育异常相关的血管生成。

Rifaximin Inhibits Small Bowel Angiodysplasia-Associated Angiogenesis by Attenuating LncRNA-HIF1A-AS2/miR-153-3p/HIF-1 α/Ang-2 Axis.

作者信息

Peng Shuai, Yin An-Ning, Liao Fei, Zhao Liang

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

出版信息

Curr Med Sci. 2025 Jun;45(3):574-584. doi: 10.1007/s11596-025-00061-z. Epub 2025 Jun 13.

DOI:10.1007/s11596-025-00061-z
PMID:40512359
Abstract

BACKGROUNDS AND OBJECTIVE

Angiopoietin-2 (Ang-2) is a promising biomarker and therapeutic target for gastrointestinal angiodysplasia (GIAD). We hypothesized that the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis plays a critical role in small bowel angiodysplasia (SBAD)-associated angiogenesis, which can be blocked by rifaximin. The purpose of this study was to investigate the expression and pro-angiogenic effects of the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 in SBAD and to evaluate the therapeutic potential of rifaximin on SBAD by targeting this axis.

METHODS

The expression and pro-angiogenic effects of lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 were analysed in SBAD tissues and human umbilical vein endothelial cells (HUVECs). The anti-angiogenic effect of rifaximin and its impact on the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis were evaluated in HUVECs.

RESULTS

Increased expression of lncRNA-HIF1A-AS2 and decreased expression of miR-153-3p were detected in SBAD tissues. LncRNA-HIF1A-AS2/miR-153-3p /HIF-1α were upstream regulators of Ang-2, and this axis was involved in angiogenesis in HUVECs. Rifaximin exerted antiangiogenic effects on HUVECs by blocking this axis.

CONCLUSIONS

The lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis is critically involved in SBAD-associated angiogenesis. Rifaximin is a potential therapeutic option for SBAD via blockade of this axis.

摘要

背景与目的

血管生成素-2（Ang-2）是胃肠道血管发育异常（GIAD）一个很有前景的生物标志物和治疗靶点。我们推测lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2轴在小肠血管发育异常（SBAD）相关血管生成中起关键作用，而利福昔明可阻断该轴。本研究旨在探讨lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2在SBAD中的表达及促血管生成作用，并评估利福昔明通过靶向该轴对SBAD的治疗潜力。

方法

分析lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2在SBAD组织和人脐静脉内皮细胞（HUVECs）中的表达及促血管生成作用。评估利福昔明在HUVECs中的抗血管生成作用及其对lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2轴的影响。

结果

在SBAD组织中检测到lncRNA-HIF1A-AS2表达增加，miR-153-3p表达降低。LncRNA-HIF1A-AS2/miR-153-3p /HIF-1α是Ang-2的上游调节因子，该轴参与HUVECs的血管生成。利福昔明通过阻断该轴对HUVECs发挥抗血管生成作用。

结论

lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2轴在SBAD相关血管生成中起关键作用。利福昔明通过阻断该轴是SBAD的一种潜在治疗选择。

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本文引用的文献

1
Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.沙利度胺治疗小肠血管发育不良所致反复出血
N Engl J Med. 2023 Nov 2;389(18):1649-1659. doi: 10.1056/NEJMoa2303706.
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Efficacy of pharmacologic treatment for treating gastrointestinal angiodysplasias-related bleeding: a systematic review and meta-analysis.药物治疗治疗胃肠道血管发育不良相关出血的疗效：系统评价和荟萃分析。
Eur J Gastroenterol Hepatol. 2022 Oct 1;34(10):1021-1030. doi: 10.1097/MEG.0000000000002414. Epub 2022 Jul 19.
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Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.
小剂量利福昔明可预防肝硬化失代偿患者的并发症并提高生存率。
Hepatol Int. 2021 Feb;15(1):155-165. doi: 10.1007/s12072-020-10117-y. Epub 2021 Jan 1.
4
Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation.沙利度胺通过靶向 EGFL6 抑制 EGFL6/PAX6 轴驱动的小肠血管畸形血管生成。
Cell Mol Life Sci. 2020 Dec;77(24):5207-5221. doi: 10.1007/s00018-020-03465-3. Epub 2020 Feb 1.
5
An overview of angiodysplasia: management and patient prospects.血管发育不良概述：管理和患者前景。
Expert Rev Gastroenterol Hepatol. 2018 Sep;12(9):863-872. doi: 10.1080/17474124.2018.1503532. Epub 2018 Aug 3.
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Emerging role of thalidomide in the treatment of gastrointestinal bleeding.沙利度胺在治疗胃肠道出血中的新作用。
Frontline Gastroenterol. 2018 Apr;9(2):98-104. doi: 10.1136/flgastro-2017-100870. Epub 2017 Nov 2.
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Effects of thalidomide on growth and VEGF-A expression in SW480 colon cancer cells.沙利度胺对SW480结肠癌细胞生长及VEGF - A表达的影响。
Oncol Lett. 2018 Mar;15(3):3313-3320. doi: 10.3892/ol.2017.7645. Epub 2017 Dec 19.
8
lncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia.lncRNAs HIF1A-AS2 通过海绵吸附 miR-153-3p 促进 HIF-1α 的上调，从而促进低氧条件下 HUVEC 的血管生成。
Biomed Pharmacother. 2017 Dec;96:165-172. doi: 10.1016/j.biopha.2017.09.113. Epub 2017 Oct 4.
9
Long-term rifaximin therapy as a primary prevention of hepatorenal syndrome.长期使用利福昔明治疗作为肝肾综合征的一级预防措施。
Eur J Gastroenterol Hepatol. 2017 Nov;29(11):1247-1250. doi: 10.1097/MEG.0000000000000967.
10
Diagnosis of symptomatic uncomplicated diverticular disease and the role of Rifaximin in management.有症状的单纯性憩室病的诊断及利福昔明在治疗中的作用。
Acta Biomed. 2017 Apr 28;88(1):25-32. doi: 10.23750/abm.v88i1.6360.