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TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy
Autophagy is involved in degenerative diseases such as osteoarthritis and disc degeneration. Although, tumor necrosis factor α-induced protein 3 (TNFAIP3) is well-known as a key regulator of inflammation and autophagy, it is still not clear whether TNFAIP3 regulates autophagy to protect from human d...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762495/ https://www.ncbi.nlm.nih.gov/pubmed/33226960 http://dx.doi.org/10.18632/aging.104160 |
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author | Chen, Jie Ma, Yufei Yang, Zhijie Lan, Haiyang Liu, Guangliang Zhang, Ye Xia, Huiqiang Wang, Xiaofang Han, Fei Tu, Xiaolin Liu, Bo |
author_facet | Chen, Jie Ma, Yufei Yang, Zhijie Lan, Haiyang Liu, Guangliang Zhang, Ye Xia, Huiqiang Wang, Xiaofang Han, Fei Tu, Xiaolin Liu, Bo |
author_sort | Chen, Jie |
collection | PubMed |
description | Autophagy is involved in degenerative diseases such as osteoarthritis and disc degeneration. Although, tumor necrosis factor α-induced protein 3 (TNFAIP3) is well-known as a key regulator of inflammation and autophagy, it is still not clear whether TNFAIP3 regulates autophagy to protect from human disc cells degeneration. We hypothesize that TNFAIP3 may also regulate autophagy to inhibit pro-inflammatory cytokines expression in human nucleus pulposus cells (NPCs). In this study, TNFAIP3 expression was increased in degenerative disc tissue as well as LPS-stimulated human NPCs, and the effect of TNFAIP3 in LPS-induced NPCs was further explored. The results demonstrated that pro-inflammatory cytokines expression in TNFAIP3-His cells was decreased, while it was increased in TNFAIP3-siRNA cells. Further molecular mechanism research showed that TNFAIP3-siRNA cells enhanced the phosphorylation of mammalian target of rapamycin (mTOR) and inhibited autophagy. Meanwhile, after treatment of TNFAIP3-siRNA cells with the mTOR inhibitor Torin1, the level of autophagy increased and the decrease of extracellular matrix was reversed. In summary, overexpressed TNFAIP3 can promote autophagy and reduce inflammation in LPS-induced human NPCs. Moreover, autophagy triggered by TNFAIP3 can ameliorate the degeneration of inflammatory human NPCs, providing a potential and an attractive therapeutic strategy for degenerative disease. |
format | Online Article Text |
id | pubmed-7762495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-77624952021-01-08 TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy Chen, Jie Ma, Yufei Yang, Zhijie Lan, Haiyang Liu, Guangliang Zhang, Ye Xia, Huiqiang Wang, Xiaofang Han, Fei Tu, Xiaolin Liu, Bo Aging (Albany NY) Research Paper Autophagy is involved in degenerative diseases such as osteoarthritis and disc degeneration. Although, tumor necrosis factor α-induced protein 3 (TNFAIP3) is well-known as a key regulator of inflammation and autophagy, it is still not clear whether TNFAIP3 regulates autophagy to protect from human disc cells degeneration. We hypothesize that TNFAIP3 may also regulate autophagy to inhibit pro-inflammatory cytokines expression in human nucleus pulposus cells (NPCs). In this study, TNFAIP3 expression was increased in degenerative disc tissue as well as LPS-stimulated human NPCs, and the effect of TNFAIP3 in LPS-induced NPCs was further explored. The results demonstrated that pro-inflammatory cytokines expression in TNFAIP3-His cells was decreased, while it was increased in TNFAIP3-siRNA cells. Further molecular mechanism research showed that TNFAIP3-siRNA cells enhanced the phosphorylation of mammalian target of rapamycin (mTOR) and inhibited autophagy. Meanwhile, after treatment of TNFAIP3-siRNA cells with the mTOR inhibitor Torin1, the level of autophagy increased and the decrease of extracellular matrix was reversed. In summary, overexpressed TNFAIP3 can promote autophagy and reduce inflammation in LPS-induced human NPCs. Moreover, autophagy triggered by TNFAIP3 can ameliorate the degeneration of inflammatory human NPCs, providing a potential and an attractive therapeutic strategy for degenerative disease. Impact Journals 2020-11-20 /pmc/articles/PMC7762495/ /pubmed/33226960 http://dx.doi.org/10.18632/aging.104160 Text en Copyright: © 2020 Chen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Chen, Jie Ma, Yufei Yang, Zhijie Lan, Haiyang Liu, Guangliang Zhang, Ye Xia, Huiqiang Wang, Xiaofang Han, Fei Tu, Xiaolin Liu, Bo TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy |
title | TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy |
title_full | TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy |
title_fullStr | TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy |
title_full_unstemmed | TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy |
title_short | TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy |
title_sort | tnfaip3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mtor signaling and promoting autophagy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762495/ https://www.ncbi.nlm.nih.gov/pubmed/33226960 http://dx.doi.org/10.18632/aging.104160 |
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