外泌体非编码RNA在肝纤维化中的作用及机制

钱南南; 唐露露; 魏涛华; 杨悦; 郝文杰; 杨文明

doi:10.3969/j.issn.1001-5256.2021.10.036

外泌体非编码RNA在肝纤维化中的作用及机制

DOI: 10.3969/j.issn.1001-5256.2021.10.036

钱南南¹,
唐露露²,
魏涛华^{1, 2},
杨悦¹,
郝文杰¹,
杨文明^{2, 3, ,}

1.
安徽中医药大学研究生院, 合肥 230038
2.
安徽中医药大学第一附属医院神经内科, 合肥 230031
3.
新安医学教育部重点实验室, 合肥 230038

基金项目:

国家自然科学基金 (81973825);

2019国家中医药管理局《中医药循证能力建设项目》 (2019XZZX-NB001);

安徽中医药大学新安医学教育部重点实验室开放基金 (2020xayx12)

详细信息

通信作者:
杨文明，yangwm8810@126.com

中图分类号: R575.2
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- 被引次数: 0
出版历程
- 收稿日期: 2021-03-01
- 录用日期: 2021-03-19
- 出版日期: 2021-10-20

Role and mechanism of exosome non-coding RNA in liver fibrosis

Nannan QIAN¹,
Lulu TANG²,
Taohua WEI^{1, 2},
Yue YANG¹,
Wenjie HAO¹,
Wenming YANG^{2, 3
, ,}

1.
Graduate School, Anhui University of Chinese Medicine, Hefei 230038, China
2.
Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
3.
Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230038, China

Research funding:

National Natural Science Foundation of China (81973825);

National Administration of Traditional Chinese Medicine: 2019 Project of building evidence based practice capacity for TCM (2019XZZX-NB001);

Open Fund of the Key Laboratory of Xin'an Medical Education Ministry of Anhui University of Traditional Chinese Medicine (2020xayx12)

摘要

摘要: 肝纤维化是多种慢性肝脏疾病发展为肝硬化的初始阶段，且是一个可逆的过程。外泌体作为能够携带包括蛋白、脂质、核酸等活性物质的一种细胞外囊泡亚群，参与细胞间的信号通讯，近年来备受关注。研究表明，外泌体中非编码RNA在肝纤维化的发生发展过程中起着重要作用。在此，探讨了外泌体长链非编码RNA(包括MALAT1、H19、GAS5、MEG3、PVT1和P21)、外泌体短链非编码RNA(包括微小RNA、小核仁RNA、PIWI-interacting RNA和小干扰RNA)、外泌体环状RNA在肝纤维化发生发展过程中的作用机制。总结了不同来源(如肝细胞、胆管细胞等)的外泌体携带非编码RNA主要通过影响肝星状细胞活化、增殖、迁移、转化等过程发挥作用。未来通过对外泌体非编码RNA的深入研究，有望为肝纤维化治疗药物寻找到潜在新靶点。
- 肝硬化 /
- 外泌体 /
- RNA, 未翻译
Abstract: Liver fibrosis is the initial stage of the development of various chronic liver diseases into liver cirrhosis and is a reversible process. As a subset of extracellular vesicles that can carry active substances such as proteins, lipids, and RNA, exosomes are involved in intercellular signal communication and have attracted more and more attention in recent years. Studies have shown that non-coding RNAs in exosomes play an important role in the development and progression of liver fibrosis. This article discusses the mechanism of action of exosome long non- coding RNAs (including MALAT1, H19, GAS5, MEG3, PVT1, and P21), exosome short non-coding RNAs (including micro-RNA, small nucleolus RNA, PIWI-interacting RNA, and small interference RNA), and exosome circular RNA in the development and progression of liver fibrosis, and it is concluded that exosomes from different sources (such as hepatocytes and cholangiocytes) carrying non-coding RNAs mainly affect the activation, proliferation, migration, and transformation of hepatic stellate cells. In-depth studies of exosome non-coding RNAs in the future are expected to find potential new targets for the treatment of liver fibrosis.
- Liver Cirrhosis /
- Exosomes /
- RNA, Untranslated

HTML全文

表 1 外泌体miRNA与肝纤维化的关系

基因	表达情况	机制	参考文献
miR-200c	上调	通过下调FOG2蛋白表达和上调PI3K/Akt信号转导途径激活肝纤维化中的HSC	[23]
miR-942	上调	通过下调BAMBI介导HSC活化	[24]
miR-302c	上调	通过抑制E6AP，来激活TGFβ诱导的有丝分裂原活化蛋白激酶信号通路促进肝纤维化	[25]
miR-182	上调	通过激活PI3K/AKT信号通路促进HSC增殖，并抑制凋亡	[26]
miR-195	上调	通过靶向Smad7激活HSC	[27]
miR-30和miR-193	下调	抑制TGFβ介导的HSC活化	[28]
miR-30	下调	通过抑制KLF11表达使HSC中的TGFβ/Smad信号转导减弱，从而促进活化的HSC逆转至静止状态	[29]
miR-326	下调	通过介导TLR4/MyD88/NF-κB信号通路抑制HSC活化	[30]
miR-21	上调	促进HSC的活化及增殖	[31-32]
	下调	通过靶向PTEN/PI3K/AKT途径促进HSC增殖并抑制其凋亡
miR-145	上调	通过靶向KLF4促进HSC活化和肝纤维化	[33-34]
	下调	通过miR-145-ZEB2-p53调控体系可能参与活化HSC的凋亡
miR-122和miR-214	下调	通过外泌体介导抑制HSC的活化，从而达到抗纤维化的作用	[35]
miR-181-5p	下调	通过外泌体介导抑制STAT3/Bcl-2-Beclin 1途径来增加自噬并减少TGFβ1诱导的肝纤维化	[37]
miR-199a-5p	下调	通过外泌体作用于CCN2，导致CCN2及其下游靶标α-SMA和Ⅰ型胶原蛋白α1的表达降低，从而发挥抗纤维化的作用	[38]
miR-223	下调	通过外泌体途径调控NLRP3和caspase-1发挥保肝作用	[39]
miR-103-3p	上调	通过外泌体介导靶向KLF4促进HSC的增殖和激活	[40]

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参考文献(55)

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