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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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.
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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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