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
作者： Xing He , Jun Xie , Dongmei Zhang , Qin Su , Xue Sai
DOI: 10.1002/HEP.27671
关键词:
摘要: Schistosomiasis is a serious parasitic disease in humans, which can lead to liver fibrosis and death. Accumulating evidence indicated that targeting the deregulated microRNAs (miRNAs) could mitigate outcomes. Here, we showed progressive hepatic schistosomiasis caused elevation of miR-21 efficient sustained inhibition by using highly tropic adeno-associated virus serotype 8 (rAAV8), protected mice against lethal schistosome infection through attenuation (HF). We demonstrated an additive role interleukin (IL)−13 transforming growth factor beta 1 (TGF-β1) up-regulating expression stellate cells (HSCs) activation mothers decapentaplegic (SMAD) proteins. Furthermore, down-regulation HSCs reversed HF enhancing SMAD7 expression, thus repressing TGF-β1/Smad IL-13/Smad pathways. Conclusion: This study suggests mechanism IL-13-mediated up-regulation highlights potential rAAV8-mediated as therapeutic intervention for fibrotic diseases, such schistosomiasis. (Hepatology 2015;61:2008–2017)
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