Luo Xufeng, Zhang Dongmei, Xie Jun, Su Qin, He Xing, Bai Ruipu, Gao Guangping, Pan Weiqing
Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Mol Ther Methods Clin Dev. 2018 Oct 10;11:73-82. doi: 10.1016/j.omtm.2018.10.002. eCollection 2018 Dec 14.
Infection with causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, , is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, . We show that infection with induces the expression of transforming growth factor β1 (TGF-β1), which in turn upregulates the expression of through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough Decoy RNAs in mice attenuated hepatic fibrosis and prevented lethality following schistosome infection. Taken together, our data highlight the potential for rAAV8-mediated inhibition of as a therapeutic strategy to treat hepatic schistosomiasis.
感染[病原体名称]会导致宿主微小RNA（miRNA）表达异常，使失调的miRNA水平恢复正常可减轻病理症状。在此，我们表明宿主miRNA[具体miRNA名称]在肝血吸虫病进展过程中显著上调。我们证明，[具体miRNA名称]的升高通过抑制其靶基因[靶基因名称]的表达在感染小鼠中诱导肝纤维化。我们表明，感染[病原体名称]会诱导转化生长因子β1（TGF-β1）的表达，而TGF-β1又通过SMAD2/3 - DROSHA介导的转录后调控上调[具体miRNA名称]的表达。此外，在小鼠中通过重组腺相关病毒8（rAAV8）介导递送 Tough Decoy RNAs抑制[具体miRNA名称]可减轻肝纤维化并预防血吸虫感染后的致死率。综上所述，我们的数据突出了rAAV8介导抑制[具体miRNA名称]作为治疗肝血吸虫病的治疗策略的潜力。
