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Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway
Clusterin is a glycoprotein that is expressed in most human tissues and found in body fluids. In our previous studies we demonstrated that clusterin has a protective effect against hepatic lipid accumulation and renal fibrosis; however, the role of clusterin in hepatic fibrosis is unknown. Here, we...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912488/ https://www.ncbi.nlm.nih.gov/pubmed/31739636 http://dx.doi.org/10.3390/cells8111442 |
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author | Seo, Hye-Young Lee, So-Hee Lee, Ji-Ha Kang, Yu Na Choi, Young-Keun Hwang, Jae Seok Park, Keun-Gyu Jang, Byoung Kuk Kim, Mi Kyung |
author_facet | Seo, Hye-Young Lee, So-Hee Lee, Ji-Ha Kang, Yu Na Choi, Young-Keun Hwang, Jae Seok Park, Keun-Gyu Jang, Byoung Kuk Kim, Mi Kyung |
author_sort | Seo, Hye-Young |
collection | PubMed |
description | Clusterin is a glycoprotein that is expressed in most human tissues and found in body fluids. In our previous studies we demonstrated that clusterin has a protective effect against hepatic lipid accumulation and renal fibrosis; however, the role of clusterin in hepatic fibrosis is unknown. Here, we examined whether clusterin had protective effects against hepatic fibrosis using in vitro and in vivo models. Clusterin was upregulated in the livers of human cirrhotic patients and in thioacetamide (TAA)-induced and bile duct ligation mouse models of liver fibrosis. Loss and overexpression of clusterin promoted and attenuated hepatic fibrosis after TAA injection, respectively. In addition, we found that clusterin attenuates hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Smad3 signaling pathways. Thus, clusterin plays an important role in hepatic fibrosis. |
format | Online Article Text |
id | pubmed-6912488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69124882020-01-02 Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway Seo, Hye-Young Lee, So-Hee Lee, Ji-Ha Kang, Yu Na Choi, Young-Keun Hwang, Jae Seok Park, Keun-Gyu Jang, Byoung Kuk Kim, Mi Kyung Cells Article Clusterin is a glycoprotein that is expressed in most human tissues and found in body fluids. In our previous studies we demonstrated that clusterin has a protective effect against hepatic lipid accumulation and renal fibrosis; however, the role of clusterin in hepatic fibrosis is unknown. Here, we examined whether clusterin had protective effects against hepatic fibrosis using in vitro and in vivo models. Clusterin was upregulated in the livers of human cirrhotic patients and in thioacetamide (TAA)-induced and bile duct ligation mouse models of liver fibrosis. Loss and overexpression of clusterin promoted and attenuated hepatic fibrosis after TAA injection, respectively. In addition, we found that clusterin attenuates hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Smad3 signaling pathways. Thus, clusterin plays an important role in hepatic fibrosis. MDPI 2019-11-14 /pmc/articles/PMC6912488/ /pubmed/31739636 http://dx.doi.org/10.3390/cells8111442 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seo, Hye-Young Lee, So-Hee Lee, Ji-Ha Kang, Yu Na Choi, Young-Keun Hwang, Jae Seok Park, Keun-Gyu Jang, Byoung Kuk Kim, Mi Kyung Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway |
title | Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway |
title_full | Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway |
title_fullStr | Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway |
title_full_unstemmed | Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway |
title_short | Clusterin Attenuates Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Downregulating the Smad3 Signaling Pathway |
title_sort | clusterin attenuates hepatic fibrosis by inhibiting hepatic stellate cell activation and downregulating the smad3 signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912488/ https://www.ncbi.nlm.nih.gov/pubmed/31739636 http://dx.doi.org/10.3390/cells8111442 |
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