MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6C(lo) Phenotype.
MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6C(lo) Phenotype.
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MiR-130a-3p 通过抑制 HSC 激活并使巨噬细胞偏向 Ly6C(lo) 表型来减轻肝纤维化
DOI：
10.3389/fimmu.2021.696069
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发表时间：
2021
影响因子：
7.3
通讯作者：
Xia CM
中科院分区：
文献类型：
--
作者：
Liu L;Wang P;Wang YS;Zhang YN;Li C;Yang ZY;Liu ZH;Zhan TZ;Xu J;Xia CM
越来越多的证据表明microRNAs（miRNAs）在肝硬化中的重要作用，但miR-130 a-3 p与肝硬化的关系尚不完全清楚。众所周知，血吸虫病是人畜共患病之一，发展到一定程度可导致肝硬化。本研究旨在探讨miR-130 a-3 p在血吸虫病肝纤维化中的生物学作用。日本血吸虫感染小鼠后，经腹腔注射，观察小鼠血吸虫感染情况。用慢病毒载体（LV）-miR-130 a-3 p通过尾静脉流体动力学注射处理。我们的研究结果显示，肝硬化患者血清和感染S.日本的结果表明，LV-miR-130 a-3 p能有效进入肝脏，减轻肝脏肉芽肿性炎症和胶原沉积。同时，LV-miR-130 a-3 p促进的巨噬细胞呈现Ly 6Clo表型，伴随着金属蛋白酶组织抑制剂（TIMP）1表达的降低，以及基质金属蛋白酶（MMP）2表达的增加，这有助于胶原的溶解。miR-130 a-3 p的过表达不仅抑制了肝星状细胞（hepatic stellate cells，HSC）的活化和增殖，而且诱导了HSC的凋亡。此外，我们还证实了miR-130 a-3 p能够与丝裂原活化蛋白激酶（MAPK）1和转化生长因子β受体（TGFBR）1和TGFBR 2基因结合并抑制这些基因的表达。提示miR-130 a-3 p有可能成为血吸虫病肝纤维化预后判断和治疗的候选生物标志物和治疗靶点。
Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasis in vivo and in vitro. The mice infected with Schistosoma japonicum (S. japonicum) were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected with S. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clo phenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.
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DOI：
10.1007/978-94-024-1079-2_39
发表时间：
2017-01-01
期刊：
TAURINE 10
影响因子：
--
作者：
Ito, Takashi;Yamamoto, Nao;Schaffer, Stephen W.
通讯作者：
Schaffer, Stephen W.
影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.
利用 MALDI-TOF 质谱和 ClinProTools 分析鉴定新发的晚期血吸虫病
影响因子：
2.9
作者：
Huang, Yuzheng;Xu, Yongliang;Hua, Haiyong
通讯作者：
Hua, Haiyong
影响因子：
4.6
作者：
Mao Y;Wang B;Xu X;Du W;Li W;Wang Y
通讯作者：
Wang Y
DOI：
10.1016/j.omtn.2018.07.005
发表时间：
2018-09-07
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Dalsgaard T;Cecchi CR;Askou AL;Bak RO;Andersen PO;Hougaard D;Jensen TG;Dagnæs-Hansen F;Mikkelsen JG;Corydon TJ;Aagaard L
通讯作者：
Aagaard L