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Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis
The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Biochemistry and Molecular Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342867/ https://www.ncbi.nlm.nih.gov/pubmed/28115038 http://dx.doi.org/10.5483/BMBRep.2017.50.2.012 |
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author | Jang, Yu Jin An, Su Yeon Kim, Jong-Hoon |
author_facet | Jang, Yu Jin An, Su Yeon Kim, Jong-Hoon |
author_sort | Jang, Yu Jin |
collection | PubMed |
description | The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the TGFβ/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated TGFβ type I receptor expression by binding to αvβ3 integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating TGFβ-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis. |
format | Online Article Text |
id | pubmed-5342867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-53428672017-04-20 Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis Jang, Yu Jin An, Su Yeon Kim, Jong-Hoon BMB Rep Perspective The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the TGFβ/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated TGFβ type I receptor expression by binding to αvβ3 integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating TGFβ-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis. Korean Society for Biochemistry and Molecular Biology 2017 2017-02-28 /pmc/articles/PMC5342867/ /pubmed/28115038 http://dx.doi.org/10.5483/BMBRep.2017.50.2.012 Text en Copyright © 2017 by the The Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Perspective Jang, Yu Jin An, Su Yeon Kim, Jong-Hoon Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
title | Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
title_full | Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
title_fullStr | Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
title_full_unstemmed | Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
title_short | Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
title_sort | identification of mfge8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342867/ https://www.ncbi.nlm.nih.gov/pubmed/28115038 http://dx.doi.org/10.5483/BMBRep.2017.50.2.012 |
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