Recombinant adeno-associated virus-mediated inhibition of microRNA-21 protects mice against the lethal schistosome infection by repressing both IL-13 and transforming growth factor beta 1 pathways.
Recombinant adeno-associated virus-mediated inhibition of microRNA-21 protects mice against the lethal schistosome infection by repressing both IL-13 and transforming growth factor beta 1 pathways.
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重组腺相关病毒介导的 microRNA-21 抑制通过抑制 IL-13 和转化生长因子 β 1 途径保护小鼠免受致命的血吸虫感染
DOI：
10.1002/hep.27671
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发表时间：
2015-06
期刊：
影响因子：
13.5
通讯作者：
Pan, Weiqing
中科院分区：
文献类型：
--
作者：
He, Xing;Xie, Jun;Zhang, Dongmei;Su, Qin;Sai, Xue;Bai, Ruipu;Chen, Chao;Luo, Xufeng;Gao, Guangping;Pan, Weiqing
血吸虫病是一种严重的人类寄生虫病，可导致肝纤维化和死亡。越来越多的证据表明，以解除管制的microRNAs为靶点可以减轻疾病后果。在这里，我们发现进行性肝血吸虫病引起miR-21的升高，并通过使用高度嗜肝性腺相关病毒8型(RAAV8)通过减轻肝纤维化来保护小鼠免受致死性血吸虫感染而有效和持续地抑制miR-21。我们证实了IL-13和转化生长因子-Smad1通过激活β蛋白上调肝星状细胞miR-21表达的相加作用。此外，肝干细胞中miR-21的下调通过增强Smad7的表达而逆转肝纤维化，从而抑制转化生长因子-β-1/Smad和IL-13/Smad信号通路。我们的研究揭示了IL-13介导的血吸虫病肝纤维化的机制是通过上调miR-21来实现的，并强调了rAAV8介导的miR-21抑制作为治疗血吸虫病等肝纤维化疾病的可能性。
Schistosomiasis is a serious parasitic disease in humans, which can lead to liver fibrosis and death. Accumulating evidence indicated that targeting the deregulated microRNAs could mitigate disease outcomes. Here, we showed that progressive hepatic schistosomiasis caused elevation of miR-21 and efficient and sustained inhibition of miR-21 by using highly hepatic tropic adeno-associated virus serotype 8 (rAAV8) protected mice against the lethal schistosome infection through the attenuation of hepatic fibrosis. We demonstrated an additive role of IL-13 and TGF-β1 in up-regulating the miR-21 expression in the hepatic stellate cells (HSCs) by activation of the SMAD proteins. Further, the down-regulation of miR-21 in the HSCs reversed hepatic fibrosis by enhancing SMAD7 expression, thus repressing TGF-β1/Smad and IL-13/Smad pathways. Our study revealed the mechanism of IL-13-mediated schistosomiasis hepatic fibrosis by up-regulation of miR-21 and highlights the potential of rAAV8-mediated miR-21 inhibition as a therapeutic intervention for hepatic fibrotic diseases, such as schistosomiasis.
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影响因子：
48
作者：
Xie, Jun;Ameres, Stefan L.;Friedline, Randall;Hung, Jui-Hung;Zhang, Yu;Xie, Qing;Zhong, Li;Su, Qin;He, Ran;Li, Mengxin;Li, Huapeng;Mu, Xin;Zhang, Hongwei;Broderick, Jennifer A.;Kim, Jason K.;Weng, Zhiping;Flotte, Terence R.;Zamore, Phillip D.;Gao, Guangping
通讯作者：
Gao, Guangping
影响因子：
64.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko
影响因子：
5.4
作者：
Gao, Guang-Ping;Lu, You;Wilson, James M.
通讯作者：
Wilson, James M.
影响因子：
5.3
作者：
Krichevsky AM;Gabriely G
通讯作者：
Gabriely G
影响因子：
20.1
作者：
Fleissner, Felix;Jazbutyte, Virginija;Thum, Thomas
通讯作者：
Thum, Thomas