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Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients
Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset an...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519014/ https://www.ncbi.nlm.nih.gov/pubmed/28604663 http://dx.doi.org/10.1038/emm.2017.69 |
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author | Li, Jinteng Wang, Peng Xie, Zhongyu Yang, Rui Li, Yuxi Wu, Xiaohua Su, Hongjun Deng, Wen Wang, Shan Liu, Zhenhua Cen, Shuizhong Ouyang, Yi Wu, Yanfeng Shen, Huiyong |
author_facet | Li, Jinteng Wang, Peng Xie, Zhongyu Yang, Rui Li, Yuxi Wu, Xiaohua Su, Hongjun Deng, Wen Wang, Shan Liu, Zhenhua Cen, Shuizhong Ouyang, Yi Wu, Yanfeng Shen, Huiyong |
author_sort | Li, Jinteng |
collection | PubMed |
description | Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions. However, the properties of MSCs from AS patients in an inflammatory environment have never been explored. Lipopolysaccharide (LPS), a proinflammatory substance derived from the outer membrane of Gram-negative bacteria, can alter the status and function of MSCs. However, whether MSCs from AS patients exhibit abnormal responses to LPS stimulation has not been reported. Autophagy is a lysosome-mediated catabolic process that participates in many physiological and pathological processes. The link between autophagy and AS remains largely unknown. The level of autophagy in ASMSCs after LPS stimulation remains to be addressed. In this study, we demonstrated that although the basal level of autophagy did not differ between MSCs from healthy donors (HDMSCs) and ASMSCs, LPS-induced autophagy was weaker in ASMSCs than in HDMSCs. Specifically, increased TRAF4 expression in ASMSCs impaired LPS-induced autophagy, potentially by inhibiting the phosphorylation of Beclin-1. These data may provide further insight into ASMSC dysfunction and the precise mechanism underlying the pathogenesis of AS. |
format | Online Article Text |
id | pubmed-5519014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55190142017-07-26 Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients Li, Jinteng Wang, Peng Xie, Zhongyu Yang, Rui Li, Yuxi Wu, Xiaohua Su, Hongjun Deng, Wen Wang, Shan Liu, Zhenhua Cen, Shuizhong Ouyang, Yi Wu, Yanfeng Shen, Huiyong Exp Mol Med Original Article Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions. However, the properties of MSCs from AS patients in an inflammatory environment have never been explored. Lipopolysaccharide (LPS), a proinflammatory substance derived from the outer membrane of Gram-negative bacteria, can alter the status and function of MSCs. However, whether MSCs from AS patients exhibit abnormal responses to LPS stimulation has not been reported. Autophagy is a lysosome-mediated catabolic process that participates in many physiological and pathological processes. The link between autophagy and AS remains largely unknown. The level of autophagy in ASMSCs after LPS stimulation remains to be addressed. In this study, we demonstrated that although the basal level of autophagy did not differ between MSCs from healthy donors (HDMSCs) and ASMSCs, LPS-induced autophagy was weaker in ASMSCs than in HDMSCs. Specifically, increased TRAF4 expression in ASMSCs impaired LPS-induced autophagy, potentially by inhibiting the phosphorylation of Beclin-1. These data may provide further insight into ASMSC dysfunction and the precise mechanism underlying the pathogenesis of AS. Nature Publishing Group 2017-06 2017-06-09 /pmc/articles/PMC5519014/ /pubmed/28604663 http://dx.doi.org/10.1038/emm.2017.69 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Original Article Li, Jinteng Wang, Peng Xie, Zhongyu Yang, Rui Li, Yuxi Wu, Xiaohua Su, Hongjun Deng, Wen Wang, Shan Liu, Zhenhua Cen, Shuizhong Ouyang, Yi Wu, Yanfeng Shen, Huiyong Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
title | Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
title_full | Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
title_fullStr | Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
title_full_unstemmed | Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
title_short | Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
title_sort | elevated traf4 expression impaired lps-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519014/ https://www.ncbi.nlm.nih.gov/pubmed/28604663 http://dx.doi.org/10.1038/emm.2017.69 |
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