UMMS Affiliation

Horae Gene Therapy Center; Department of Microbiology and Physiological Systems

Publication Date

2018-10-10

Document Type

Article

Disciplines

Digestive System Diseases | Hepatology | Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Infectious Disease | Molecular Biology | Parasitic Diseases | Parasitology | Translational Medical Research

Abstract

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.

Keywords

TGF-β/Smad7, hepatic stellate cell, microRNA, schistosomiasis, UMCCTS funding

Rights and Permissions

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

10.1016/j.omtm.2018.10.002

Source

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

Journal/Book/Conference Title

Molecular therapy. Methods and clinical development

Related Resources

Link to Article in PubMed

PubMed ID

30406154

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.