Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xiao, Ting, Meng, Wen, Jin, Zhangliu, Wang, Jing, Deng, Jiangming, Wen, Jie, Liu, Bilian, Liu, Meilian, Bai, Juli, Liu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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
_version_ 1784761034984128512
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
work_keys_str_mv AT xiaoting mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT mengwen mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT jinzhangliu mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT wangjing mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT dengjiangming mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT wenjie mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT liubilian mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT liumeilian mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT baijuli mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration
AT liufeng mir1825ppromoteshepatocytestellatecellcrosstalktofacilitateliverregeneration