Hsa_circ_0109623 regulates the progression of autoimmune liver disease through Hsa_miR_146b-3p/Sortilin 1-mediated activation of CD4+ T cells.

IF 5.6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Communications Pub Date : 2025-01-07 eCollection Date: 2025-01-01 DOI:10.1097/HC9.0000000000000607

Xinliang Lv, Li Zhu, Shijie Feng, Siyu Yang, Guohua Li, Jinqin Zhan, Yuchun Tan, Yuquan Liu, Jinliang Zhang, Yujin Wang, Yucheng Cheng, Ping Fu, Yushan Xu, Chenhong Zheng

{"title":"Hsa_circ_0109623 regulates the progression of autoimmune liver disease through Hsa_miR_146b-3p/Sortilin 1-mediated activation of CD4+ T cells.","authors":"Xinliang Lv, Li Zhu, Shijie Feng, Siyu Yang, Guohua Li, Jinqin Zhan, Yuchun Tan, Yuquan Liu, Jinliang Zhang, Yujin Wang, Yucheng Cheng, Ping Fu, Yushan Xu, Chenhong Zheng","doi":"10.1097/HC9.0000000000000607","DOIUrl":null,"url":null,"abstract":"Background: Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated liver inflammation. Despite its global prevalence, the pathogenesis of AIH remains poorly understood, and there is a lack of specific biomarkers and targeted treatments. This study aimed to investigate the role of hsa_circ_0109623, hsa-miR-146b-3p, and Sortilin 1 (SORT1) in AIH and their potential as therapeutic targets.Methods: We collected liver tissue samples and peripheral blood mononuclear cells from patients with AIH and healthy controls and performed RT-PCR, western blotting, flow cytometry, and other molecular biology techniques to analyze the expression of hsa_circ_0109623, hsa-miR-146b-3p, and SORT1. We also used bioinformatics tools to predict the interaction between these molecules and conducted luciferase reporter assays to confirm their binding.Results: hsa_circ_0109623 was significantly upregulated in patients with AIH and positively correlated with inflammatory activity. We also found that hsa_circ_0109623 could enhance CD4+ T-cell activation and promote the expression of proinflammatory cytokines. Conversely, hsa-miR-146b-3p was downregulated in patients with AIH and negatively correlated with the expression of hsa_circ_0109623 and SORT1. In addition, hsa-miR-146b-3p acted as a sponge for hsa_circ_0109623, inhibiting CD4+ Th1 cell polarization and cytokine production. SORT1 was also upregulated in patients with AIH and acted as a sponge for hsa-miR-146b-3p, promoting CD4+ Th1 cell polarization and cytokine expression. Furthermore, hsa_miR_146b-3p/SORT1 can regulate the STAT1/STAT4 signaling pathway mediating the progression of AIH.Conclusions: The hsa_circ_0109623/hsa-miR-146b-3p/SORT1 axis plays a crucial role in the pathogenesis of AIH by regulating CD4+ T-cell activation and cytokine production. These molecules may serve as potential biomarkers and therapeutic targets for AIH. Further research is needed to validate these findings and explore their clinical applications.","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 1","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717529/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Communications","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/HC9.0000000000000607","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated liver inflammation. Despite its global prevalence, the pathogenesis of AIH remains poorly understood, and there is a lack of specific biomarkers and targeted treatments. This study aimed to investigate the role of hsa_circ_0109623, hsa-miR-146b-3p, and Sortilin 1 (SORT1) in AIH and their potential as therapeutic targets.

Methods: We collected liver tissue samples and peripheral blood mononuclear cells from patients with AIH and healthy controls and performed RT-PCR, western blotting, flow cytometry, and other molecular biology techniques to analyze the expression of hsa_circ_0109623, hsa-miR-146b-3p, and SORT1. We also used bioinformatics tools to predict the interaction between these molecules and conducted luciferase reporter assays to confirm their binding.

Results: hsa_circ_0109623 was significantly upregulated in patients with AIH and positively correlated with inflammatory activity. We also found that hsa_circ_0109623 could enhance CD4+ T-cell activation and promote the expression of proinflammatory cytokines. Conversely, hsa-miR-146b-3p was downregulated in patients with AIH and negatively correlated with the expression of hsa_circ_0109623 and SORT1. In addition, hsa-miR-146b-3p acted as a sponge for hsa_circ_0109623, inhibiting CD4+ Th1 cell polarization and cytokine production. SORT1 was also upregulated in patients with AIH and acted as a sponge for hsa-miR-146b-3p, promoting CD4+ Th1 cell polarization and cytokine expression. Furthermore, hsa_miR_146b-3p/SORT1 can regulate the STAT1/STAT4 signaling pathway mediating the progression of AIH.

Conclusions: The hsa_circ_0109623/hsa-miR-146b-3p/SORT1 axis plays a crucial role in the pathogenesis of AIH by regulating CD4+ T-cell activation and cytokine production. These molecules may serve as potential biomarkers and therapeutic targets for AIH. Further research is needed to validate these findings and explore their clinical applications.

查看原文本刊更多论文

Hsa_circ_0109623通过Hsa_miR_146b-3p/Sortilin 1介导的CD4+ T细胞活化调节自身免疫性肝病的进展。

背景：自身免疫性肝炎（AIH）是一种以免疫介导的肝脏炎症为特征的慢性肝病。尽管AIH在全球流行，但其发病机制仍然知之甚少，并且缺乏特异性的生物标志物和靶向治疗。本研究旨在探讨hsa_circ_0109623、hsa-miR-146b-3p和SORT1在AIH中的作用及其作为治疗靶点的潜力。方法：收集AIH患者和健康对照者的肝组织样本和外周血单核细胞，采用RT-PCR、western blotting、流式细胞术等分子生物学技术分析hsa_circ_0109623、hsa-miR-146b-3p和SORT1的表达。我们还使用生物信息学工具来预测这些分子之间的相互作用，并进行荧光素酶报告基因测定来确认它们的结合。结果：hsa_circ_0109623在AIH患者中表达显著上调，且与炎症活动呈正相关。我们还发现hsa_circ_0109623可以增强CD4+ t细胞的活化，促进促炎细胞因子的表达。相反，hsa-miR-146b-3p在AIH患者中下调，与hsa_circ_0109623和SORT1的表达呈负相关。此外，hsa-miR-146b-3p作为hsa_circ_0109623的海绵，抑制CD4+ Th1细胞极化和细胞因子的产生。SORT1在AIH患者中也上调，并作为hsa-miR-146b-3p的海绵，促进CD4+ Th1细胞极化和细胞因子表达。此外，hsa_miR_146b-3p/SORT1可以调控介导AIH进展的STAT1/STAT4信号通路。结论：hsa_circ_0109623/hsa-miR-146b-3p/SORT1轴通过调节CD4+ t细胞活化和细胞因子的产生，在AIH的发病过程中起着至关重要的作用。这些分子可能作为AIH的潜在生物标志物和治疗靶点。需要进一步的研究来验证这些发现并探索其临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

8.00

自引率

2.00%

发文量

248

审稿时长

8 weeks

期刊介绍： Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction.