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The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are a group of multipotent cells with key properties of multi-lineage differentiation, expressing a set of relatively specific surface markers and unique immunomodulatory functions. IDO1, a catabolic enzyme of tryptophan, represents a critical molecule mediating immunom...

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Autores principales: Na, Tao, Liu, Jing, Zhang, Kehua, Ding, Min, Yuan, Bao-Zhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334899/
https://www.ncbi.nlm.nih.gov/pubmed/25692676
http://dx.doi.org/10.1371/journal.pone.0118168
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author Na, Tao
Liu, Jing
Zhang, Kehua
Ding, Min
Yuan, Bao-Zhu
author_facet Na, Tao
Liu, Jing
Zhang, Kehua
Ding, Min
Yuan, Bao-Zhu
author_sort Na, Tao
collection PubMed
description Mesenchymal stem cells (MSCs) are a group of multipotent cells with key properties of multi-lineage differentiation, expressing a set of relatively specific surface markers and unique immunomodulatory functions. IDO1, a catabolic enzyme of tryptophan, represents a critical molecule mediating immunomodulatory functions of MSCs. However, the signaling pathways involved in regulating these key properties still remain elusive. To investigate the involvement of Notch signaling as well as other potential signaling pathway(s) in regulating these critical properties of MSCs, we treated human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with γ-secreatase inhibitor I (GSI-I), which inhibits both Notch signaling and ubiquitin-proteasome activities. It was shown that the GSI-I treatment resulted in apoptosis, reduced expression of surface markers CD73, CD90 and CD105, reduced osteogenic differentiation, and reduction of the hUC-MSCs-mediated suppression of Th1 lymphocyte proliferation and the IFN-γ-induced IDO1 expression. Through distinguishing the effects of GSI-I between Notch inhibition and proteasome inhibition, it was further observed that, whereas both Notch inhibition and proteasome inhibition were attributable to the reduced CD105 expression and osteogenic differentiation, but not to the induced apoptosis. However, Notch inhibition, but not proteasome inhibition, only contributed to the significant effect of GSI-I on Th1 proliferation probably through reducing IDO1 promoter activity. In conclusion, the Notch signaling may represent a very important cell signaling capable of regulating multiple critical properties, especially the immunomodulatory functions of MSCs.
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spelling pubmed-43348992015-02-24 The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells Na, Tao Liu, Jing Zhang, Kehua Ding, Min Yuan, Bao-Zhu PLoS One Research Article Mesenchymal stem cells (MSCs) are a group of multipotent cells with key properties of multi-lineage differentiation, expressing a set of relatively specific surface markers and unique immunomodulatory functions. IDO1, a catabolic enzyme of tryptophan, represents a critical molecule mediating immunomodulatory functions of MSCs. However, the signaling pathways involved in regulating these key properties still remain elusive. To investigate the involvement of Notch signaling as well as other potential signaling pathway(s) in regulating these critical properties of MSCs, we treated human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with γ-secreatase inhibitor I (GSI-I), which inhibits both Notch signaling and ubiquitin-proteasome activities. It was shown that the GSI-I treatment resulted in apoptosis, reduced expression of surface markers CD73, CD90 and CD105, reduced osteogenic differentiation, and reduction of the hUC-MSCs-mediated suppression of Th1 lymphocyte proliferation and the IFN-γ-induced IDO1 expression. Through distinguishing the effects of GSI-I between Notch inhibition and proteasome inhibition, it was further observed that, whereas both Notch inhibition and proteasome inhibition were attributable to the reduced CD105 expression and osteogenic differentiation, but not to the induced apoptosis. However, Notch inhibition, but not proteasome inhibition, only contributed to the significant effect of GSI-I on Th1 proliferation probably through reducing IDO1 promoter activity. In conclusion, the Notch signaling may represent a very important cell signaling capable of regulating multiple critical properties, especially the immunomodulatory functions of MSCs. Public Library of Science 2015-02-18 /pmc/articles/PMC4334899/ /pubmed/25692676 http://dx.doi.org/10.1371/journal.pone.0118168 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Na, Tao
Liu, Jing
Zhang, Kehua
Ding, Min
Yuan, Bao-Zhu
The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells
title The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells
title_full The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells
title_fullStr The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells
title_full_unstemmed The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells
title_short The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells
title_sort notch signaling regulates cd105 expression, osteogenic differentiation and immunomodulation of human umbilical cord mesenchymal stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334899/
https://www.ncbi.nlm.nih.gov/pubmed/25692676
http://dx.doi.org/10.1371/journal.pone.0118168
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