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MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression
Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family me...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804167/ https://www.ncbi.nlm.nih.gov/pubmed/27001906 http://dx.doi.org/10.1038/ncomms10993 |
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author | Hyun, Jeongeun Wang, Sihyung Kim, Jieun Rao, Kummara Madhusudana Park, Soo Yong Chung, Ildoo Ha, Chang-Sik Kim, Sang-Woo Yun, Yang H. Jung, Youngmi |
author_facet | Hyun, Jeongeun Wang, Sihyung Kim, Jieun Rao, Kummara Madhusudana Park, Soo Yong Chung, Ildoo Ha, Chang-Sik Kim, Sang-Woo Yun, Yang H. Jung, Youngmi |
author_sort | Hyun, Jeongeun |
collection | PubMed |
description | Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a-3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl(4))-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactivation marker of HSCs, in CCl(4)-treated liver. Smo blocks transcriptional expression of miR-378a-3p by activating the p65 subunit of nuclear factor-κB (NF-κB). The hepatic level of miR-378a-3p is inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocellular carcinoma. Our results demonstrate that miR-378a-3p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF-κB signalling, suggesting miR-378a-3p has therapeutic potential for liver fibrosis. |
format | Online Article Text |
id | pubmed-4804167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48041672016-03-25 MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression Hyun, Jeongeun Wang, Sihyung Kim, Jieun Rao, Kummara Madhusudana Park, Soo Yong Chung, Ildoo Ha, Chang-Sik Kim, Sang-Woo Yun, Yang H. Jung, Youngmi Nat Commun Article Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a-3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl(4))-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactivation marker of HSCs, in CCl(4)-treated liver. Smo blocks transcriptional expression of miR-378a-3p by activating the p65 subunit of nuclear factor-κB (NF-κB). The hepatic level of miR-378a-3p is inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocellular carcinoma. Our results demonstrate that miR-378a-3p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF-κB signalling, suggesting miR-378a-3p has therapeutic potential for liver fibrosis. Nature Publishing Group 2016-03-22 /pmc/articles/PMC4804167/ /pubmed/27001906 http://dx.doi.org/10.1038/ncomms10993 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Hyun, Jeongeun Wang, Sihyung Kim, Jieun Rao, Kummara Madhusudana Park, Soo Yong Chung, Ildoo Ha, Chang-Sik Kim, Sang-Woo Yun, Yang H. Jung, Youngmi MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression |
title | MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression |
title_full | MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression |
title_fullStr | MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression |
title_full_unstemmed | MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression |
title_short | MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression |
title_sort | microrna-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing gli3 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804167/ https://www.ncbi.nlm.nih.gov/pubmed/27001906 http://dx.doi.org/10.1038/ncomms10993 |
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