UMMS Affiliation

Department of Medicine

Publication Date

2021-05-14

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Digestive System Diseases | Gastroenterology

Abstract

microRNAs (miRs) are small regulatory RNAs that are frequently deregulated in liver disease. Liver fibrosis is characterized by excessive scarring caused by chronic inflammatory processes. In this study, we determined the functional role of miR-132 using a locked nucleic acid (LNA)-anti-miR approach in liver fibrosis. A significant induction in miR-132 levels was found in mice treated with CCl4 and in patients with fibrosis/cirrhosis. Inhibition of miR-132 in mice with LNA-anti-miR-132 caused decreases in CCl4-induced fibrogenesis and inflammatory phenotype. An attenuation in collagen fibers, alpha SMA, MCP1, IL-1beta, and Cox2 was found in LNA-anti-miR-132-treated mice. CCl4 treatment increased caspase 3 activity and extracellular vesicles (EVs) in control but not in anti-miR-132-treated mice. Inhibition of miR-132 was associated with augmentation of MMP12 in the liver and Kupffer cells. In vivo and in vitro studies suggest miR-132 targets SIRT1 and inflammatory genes. Using tumor cancer genome atlas data, an increase in miR-132 was found in hepatocellular carcinoma (HCC). Increased miR-132 levels were associated with fibrogenic genes, higher tumor grade and stage, and unfavorable survival in HCC patients. Therapeutic inhibition of miR-132 might be a new approach to alleviate liver fibrosis, and treatment efficacy can be monitored by observing EV shedding.

Keywords

Kupffer cells, extracellular vesicles, inflammation, liver fibrosis, locked nucleic acid, microRNA-132

Rights and Permissions

Copyright 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

DOI of Published Version

10.1016/j.omtn.2021.05.007

Source

Momen-Heravi F, Catalano D, Talis A, Szabo G, Bala S. Protective effect of LNA-anti-miR-132 therapy on liver fibrosis in mice. Mol Ther Nucleic Acids. 2021 May 14;25:155-167. doi: 10.1016/j.omtn.2021.05.007. PMID: 34458001; PMCID: PMC8368790. Link to article on publisher's site

Journal/Book/Conference Title

Molecular therapy. Nucleic acids

Related Resources

Link to Article in PubMed

PubMed ID

34458001

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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