Horae Gene Therapy Center; Department of Microbiology and Physiological Systems
Digestive System Diseases | Hepatology | Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Infectious Disease | Molecular Biology | Parasitic Diseases | Parasitology | Translational Medical Research
Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 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 miR-96 as a therapeutic strategy to treat hepatic schistosomiasis.
TGF-β/Smad7, hepatic stellate cell, microRNA, schistosomiasis, UMCCTS funding
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Copyright 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Mol Ther Methods Clin Dev. 2018 Oct 10;11:73-82. doi: 10.1016/j.omtm.2018.10.002. eCollection 2018 Dec 14. Link to article on publisher's site
Molecular therapy. Methods and clinical development
Luo, Xufeng; Zhang, Dongmei; Xie, Jun; Su, Qin; He, Xing; Bai, Ruipu; Gao, Guangping; and Pan, Weiqing, "MicroRNA-96 Promotes Schistosomiasis Hepatic Fibrosis in Mice by Suppressing Smad7" (2018). UMass Center for Clinical and Translational Science Supported Publications. 156.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Digestive System Diseases Commons, Hepatology Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Immunoprophylaxis and Therapy Commons, Infectious Disease Commons, Molecular Biology Commons, Parasitic Diseases Commons, Parasitology Commons, Translational Medical Research Commons