Hepatology communications · 2025
Hsa_circ_0109623 regulates the progression of autoimmune liver disease through Hsa_miR_146b-3p/Sortilin 1-mediated activation of CD4+ T cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lv Xinliang, Zhu Li, Feng Shijie, Yang Siyu, Li Guohua, Zhan Jinqin, Tan Yuchun, Liu Yuquan, Zhang Jinliang, Wang Yujin, Cheng Yucheng, Fu Ping, Xu Yushan, Zheng Chenhong
Аннотация
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.
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.