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miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration
A unique feature of the liver is its high regenerative capacity, which is essential to maintain liver homeostasis. However, key regulators of liver regeneration (LR) remain ill-defined. Here, we identify hepatic miR-182-5p as a key regulator of LR. Suppressing miR-182-5p, whose expression is signifi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343643/ https://www.ncbi.nlm.nih.gov/pubmed/35915318 http://dx.doi.org/10.1038/s42003-022-03714-0 |
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author | Xiao, Ting Meng, Wen Jin, Zhangliu Wang, Jing Deng, Jiangming Wen, Jie Liu, Bilian Liu, Meilian Bai, Juli Liu, Feng |
author_facet | Xiao, Ting Meng, Wen Jin, Zhangliu Wang, Jing Deng, Jiangming Wen, Jie Liu, Bilian Liu, Meilian Bai, Juli Liu, Feng |
author_sort | Xiao, Ting |
collection | PubMed |
description | A unique feature of the liver is its high regenerative capacity, which is essential to maintain liver homeostasis. However, key regulators of liver regeneration (LR) remain ill-defined. Here, we identify hepatic miR-182-5p as a key regulator of LR. Suppressing miR-182-5p, whose expression is significantly induced in the liver of mice post two-thirds partial hepatectomy (PH), abrogates PH-induced LR in mice. In contrast, liver-specific overexpression of miR-182-5p promotes LR in mice with PH. Overexpression of miR-182-5p failed to promote proliferation in hepatocytes, but stimulates proliferation when hepatocytes are cocultured with stellate cells. Mechanistically, miR-182-5p stimulates Cyp7a1-mediated cholic acid production in hepatocytes, which promotes hedgehog (Hh) ligand production in stellate cells, leading to the activation of Hh signaling in hepatocytes and consequent cell proliferation. Collectively, our study identified miR-182-5p as a critical regulator of LR and uncovers a Cyp7a1/cholic acid-dependent mechanism by which hepatocytes crosstalk to stellate cells to facilitate LR. |
format | Online Article Text |
id | pubmed-9343643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93436432022-08-03 miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration Xiao, Ting Meng, Wen Jin, Zhangliu Wang, Jing Deng, Jiangming Wen, Jie Liu, Bilian Liu, Meilian Bai, Juli Liu, Feng Commun Biol Article A unique feature of the liver is its high regenerative capacity, which is essential to maintain liver homeostasis. However, key regulators of liver regeneration (LR) remain ill-defined. Here, we identify hepatic miR-182-5p as a key regulator of LR. Suppressing miR-182-5p, whose expression is significantly induced in the liver of mice post two-thirds partial hepatectomy (PH), abrogates PH-induced LR in mice. In contrast, liver-specific overexpression of miR-182-5p promotes LR in mice with PH. Overexpression of miR-182-5p failed to promote proliferation in hepatocytes, but stimulates proliferation when hepatocytes are cocultured with stellate cells. Mechanistically, miR-182-5p stimulates Cyp7a1-mediated cholic acid production in hepatocytes, which promotes hedgehog (Hh) ligand production in stellate cells, leading to the activation of Hh signaling in hepatocytes and consequent cell proliferation. Collectively, our study identified miR-182-5p as a critical regulator of LR and uncovers a Cyp7a1/cholic acid-dependent mechanism by which hepatocytes crosstalk to stellate cells to facilitate LR. Nature Publishing Group UK 2022-08-01 /pmc/articles/PMC9343643/ /pubmed/35915318 http://dx.doi.org/10.1038/s42003-022-03714-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Xiao, Ting Meng, Wen Jin, Zhangliu Wang, Jing Deng, Jiangming Wen, Jie Liu, Bilian Liu, Meilian Bai, Juli Liu, Feng miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
title | miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
title_full | miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
title_fullStr | miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
title_full_unstemmed | miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
title_short | miR-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
title_sort | mir-182-5p promotes hepatocyte-stellate cell crosstalk to facilitate liver regeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343643/ https://www.ncbi.nlm.nih.gov/pubmed/35915318 http://dx.doi.org/10.1038/s42003-022-03714-0 |
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