β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix
Hepatic fibrosis is a disease of the wound-healing response following chronic liver injury, and activated hepatic stellate cells (HSCs) play a crucial role in the progression of hepatic fibrosis. β-arrestin2 functions as a multiprotein scaffold to coordinate complex signal transduction networks. Alt...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242363/ https://www.ncbi.nlm.nih.gov/pubmed/32439968 http://dx.doi.org/10.1038/s41419-020-2596-8 |
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author | Sun, Wu-Yi Gu, Yuan-Jing Li, Xin-Ran Sun, Jia-Chang Du, Jia-Jia Chen, Jing-Yu Ma, Yang Wang, Qing-Tong Wei, Wei |
author_facet | Sun, Wu-Yi Gu, Yuan-Jing Li, Xin-Ran Sun, Jia-Chang Du, Jia-Jia Chen, Jing-Yu Ma, Yang Wang, Qing-Tong Wei, Wei |
author_sort | Sun, Wu-Yi |
collection | PubMed |
description | Hepatic fibrosis is a disease of the wound-healing response following chronic liver injury, and activated hepatic stellate cells (HSCs) play a crucial role in the progression of hepatic fibrosis. β-arrestin2 functions as a multiprotein scaffold to coordinate complex signal transduction networks. Although β-arrestin2 transduces diverse signals in cells, little is known about its involvement in the regulation of liver fibrosis. Our current study utilized a porcine serum-induced liver fibrosis model and found increased expression of β-arrestin2 in hepatic tissues with the progression of hepatic fibrosis, which was positively correlated with collagen levels. Furthermore, changes in human fibrotic samples were also observed. We next used β-arrestin2(−/−) mice to demonstrate that β-arrestin2 deficiency ameliorates CCl(4)-induced liver fibrosis and decreases collagen deposition. The in vitro depletion and overexpression experiments showed that decreased β-arrestin2 inhibited HSCs collagen production and elevated TβRIII expression, thus downregulating the TGF-β1 pathway components Smad2, Smad3 and Akt. These findings suggest that β-arrestin2 deficiency ameliorates liver fibrosis in mice, and β-arrestin2 may be a potential treatment target in hepatic fibrosis. |
format | Online Article Text |
id | pubmed-7242363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72423632020-05-29 β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix Sun, Wu-Yi Gu, Yuan-Jing Li, Xin-Ran Sun, Jia-Chang Du, Jia-Jia Chen, Jing-Yu Ma, Yang Wang, Qing-Tong Wei, Wei Cell Death Dis Article Hepatic fibrosis is a disease of the wound-healing response following chronic liver injury, and activated hepatic stellate cells (HSCs) play a crucial role in the progression of hepatic fibrosis. β-arrestin2 functions as a multiprotein scaffold to coordinate complex signal transduction networks. Although β-arrestin2 transduces diverse signals in cells, little is known about its involvement in the regulation of liver fibrosis. Our current study utilized a porcine serum-induced liver fibrosis model and found increased expression of β-arrestin2 in hepatic tissues with the progression of hepatic fibrosis, which was positively correlated with collagen levels. Furthermore, changes in human fibrotic samples were also observed. We next used β-arrestin2(−/−) mice to demonstrate that β-arrestin2 deficiency ameliorates CCl(4)-induced liver fibrosis and decreases collagen deposition. The in vitro depletion and overexpression experiments showed that decreased β-arrestin2 inhibited HSCs collagen production and elevated TβRIII expression, thus downregulating the TGF-β1 pathway components Smad2, Smad3 and Akt. These findings suggest that β-arrestin2 deficiency ameliorates liver fibrosis in mice, and β-arrestin2 may be a potential treatment target in hepatic fibrosis. Nature Publishing Group UK 2020-05-21 /pmc/articles/PMC7242363/ /pubmed/32439968 http://dx.doi.org/10.1038/s41419-020-2596-8 Text en © The Author(s) 2020 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/. |
spellingShingle | Article Sun, Wu-Yi Gu, Yuan-Jing Li, Xin-Ran Sun, Jia-Chang Du, Jia-Jia Chen, Jing-Yu Ma, Yang Wang, Qing-Tong Wei, Wei β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
title | β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
title_full | β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
title_fullStr | β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
title_full_unstemmed | β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
title_short | β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
title_sort | β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242363/ https://www.ncbi.nlm.nih.gov/pubmed/32439968 http://dx.doi.org/10.1038/s41419-020-2596-8 |
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