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miRNAs在肝纤维化中的作用机制

黄璐 吴有斌 倪毅然 刘梦媛 吴江锋 张艳琼

黄璐, 吴有斌, 倪毅然, 刘梦媛, 吴江锋, 张艳琼. miRNAs在肝纤维化中的作用机制[J]. 协和医学杂志, 2023, 14(6): 1251-1257. doi: 10.12290/xhyxzz.2023-0125
引用本文: 黄璐, 吴有斌, 倪毅然, 刘梦媛, 吴江锋, 张艳琼. miRNAs在肝纤维化中的作用机制[J]. 协和医学杂志, 2023, 14(6): 1251-1257. doi: 10.12290/xhyxzz.2023-0125
HUANG Lu, WU Youbin, NI Yiran, LIU Mengyuan, WU Jiangfeng, ZHANG Yanqiong. The Mechanism of miRNAs in Liver Fibrosis[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(6): 1251-1257. doi: 10.12290/xhyxzz.2023-0125
Citation: HUANG Lu, WU Youbin, NI Yiran, LIU Mengyuan, WU Jiangfeng, ZHANG Yanqiong. The Mechanism of miRNAs in Liver Fibrosis[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(6): 1251-1257. doi: 10.12290/xhyxzz.2023-0125

miRNAs在肝纤维化中的作用机制

doi: 10.12290/xhyxzz.2023-0125
基金项目: 

国家自然科学基金 81670555

详细信息
    通讯作者:

    张艳琼, E-mail: 1512575383@qq.com

  • 中图分类号: Q527+.1; R34

The Mechanism of miRNAs in Liver Fibrosis

Funds: 

National Natural Science Foundation of China 81670555

More Information
  • 摘要: 微RNA(microRNAs,miRNAs)可稳定存在于细胞、组织及血液中,参与多种疾病的病理过程,成为多种疾病诊断的潜在生物标志物。已有研究表明,其在各种慢性肝病所致的肝纤维化中发挥重要作用,可通过调节肝纤维化相关基因的表达,干预肝纤维化发展进程。本文就miRNA在肝纤维化中的作用机制作一综述,以期为肝纤维化的诊断及分子靶向治疗提供借鉴。
    作者贡献:黄璐、吴有斌、刘梦媛负责论文撰写;倪毅然负责论文构思;吴江锋、张艳琼负责论文修订。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1  肝纤维化相关miRNAs作用靶点

    TGF:转化生长因子;Gramlin:骨形态形成蛋白拮抗家族;LOX:赖氨酰氧化酶;Itga:整合素家族;Acot 4:酰基辅酶A硫酯酶4;Menin:MEN1基因的表达产物;COL:胶原蛋白;PDGFC:血小板衍生生长因子C;P4HA1:脯氨酰4-羟化酶亚基α-1;FN1:纤连蛋白1;c-Abl:非受体酪氨酸激酶Abelson超家族成员;SHIP1:含SH2结构域的肌醇5-磷酸酶;PPAR:过氧化物酶体增殖物激活受体;Twist:转录因子蛋白;ACSL:酰基辅酶A合成酶长链蛋白;SIRT1:NAD+依赖的蛋白去乙酰化酶;TGIF2:TGF-β诱导因子同源异构体2;CAV:小窝蛋白;CDKN:细胞周期蛋白依赖性激酶抑制剂;TIMP:组织基质金属蛋白酶抑制剂;PTEN:抑癌基因;E-cad:上皮细胞钙粘素

    表  1  肝纤维化相关miRNAs

    miRNAs 类别 染色体定位 种子序列 细胞类型 疾病模型 表达水平
    miR-23[9, 46-47] 抗肝纤维化 19p13.12;
    9q22.32
    UCACAUU;
    UCACAGU;
    GGCUCAG
    HSCs;肝细胞;
    胆管上皮细胞
    CCl4引起的肝纤维化、NASH;硬化性胆管炎 CHC患者血清中下降
    miR-29[12-14] 抗肝纤维化 7q32.3;
    1q32.2
    AGCACCA HSCs; CCl4等多种肝纤维化模型 CHC患者血清中上升,与肝纤维化程度呈正相关
    miR-122[17-24] 抗肝纤维化 18q21.31 GGAGUGU 肝细胞;HSCs NAFLD CHC患者血清中上升,与肝纤维化程度呈正相关
    miR-34[24-29, 48-51] 促肝纤维化 1p36.22;
    11q23.1
    GGCAGUG HSCs;肝细胞;
    胆管上皮细胞
    CCl4等多种肝纤维化模型;原发性胆管炎;NASH CHC患者血清中上升,与肝纤维化程度呈正相关
    miR-199[30-32] 促肝纤维化 19p13.2;
    1q24.3;
    9q34.11
    CCAGUGU;
    CAGUAGU
    HSCs CCl4等多种肝纤维化模型 CHC患者血清中上升,与肝纤维化程度呈正相关
    miR-221/222[34-40] 促肝纤维化 Xp11.3 GCUACAU HSCs;肝细胞;
    巨噬细胞
    CCl4等多种肝纤维化模型 多种肝纤维化模型组织表达上升
    miR-155[41-45] 双向作用 21q21.3 UAAUGCU 巨噬细胞;淋巴细
    胞;HSCs;肝细胞
    酒精性脂肪性肝炎和多种肝纤维化模型; 血清中上升,与肝纤维化程度呈正相关
    HSCs:肝星状细胞;CCl4: 四氯化碳;NASH:非酒精性脂肪性肝炎;CHC:慢性丙型肝炎;NAFLD:非酒精性脂肪性肝病;AGTR:血管紧张素Ⅱ受体;TCF4:T细胞因子4
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  • 收稿日期:  2023-03-13
  • 录用日期:  2023-04-03
  • 刊出日期:  2023-11-30

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