TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy.
TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy.
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DOI：
10.18632/aging.104160
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发表时间：
2020-11-20
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
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作者：
Chen J;Ma Y;Yang Z;Lan H;Liu G;Zhang Y;Xia H;Wang X;Han F;Tu X;Liu B
自噬参与退行性疾病，如骨关节炎和椎间盘退变。虽然肿瘤坏死因子α-诱导蛋白3 （tumor necrosis factor α-induced protein 3, TNFAIP3）是众所周知的炎症和自噬的关键调节因子，但TNFAIP3是否调节自噬以保护人类椎间盘细胞退变尚不清楚。我们假设TNFAIP3也可能调节自噬以抑制人髓核细胞（NPCs）的促炎细胞因子的表达。本研究发现，TNFAIP3在退行性椎间盘组织和lps刺激的人NPCs中表达升高，进一步探讨了TNFAIP3在lps诱导的NPCs中的作用。结果表明，促炎细胞因子在TNFAIP3-His细胞中表达降低，而在TNFAIP3-siRNA细胞中表达升高。进一步的分子机制研究表明，TNFAIP3-siRNA细胞增强了哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化，抑制了自噬。同时，用mTOR抑制剂Torin1处理TNFAIP3-siRNA细胞后，自噬水平升高，细胞外基质减少发生逆转。综上所述，在lps诱导的人类npc中，过表达TNFAIP3可以促进自噬，减轻炎症。此外，由TNFAIP3引发的自噬可以改善人类炎性npc的变性，为退行性疾病提供了一种潜在的、有吸引力的治疗策略。
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.
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影响因子：
20.3
作者：
Chu, Yuanyuan;Vahl, J. Christoph;Schmidt-Supprian, Marc
通讯作者：
Schmidt-Supprian, Marc
影响因子：
4.8
作者：
Jansen, H. J.;van Essen, P.;Stienstra, R.
通讯作者：
Stienstra, R.
DOI：
10.19540/j.cnki.cjcmm.20190111.002
发表时间：
2019-04-01
期刊：
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
影响因子：
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作者：
Ji, Qi-Jian;Sun, Zhao-Rui;Nie, Shi-Nan
通讯作者：
Nie, Shi-Nan
椎间盘变性中的遗传因素。
影响因子：
6.8
作者：
Feng, Yi;Egan, Brian;Wang, Jinxi
通讯作者：
Wang, Jinxi
DOI：
10.1038/nrrheum.2013.160
发表时间：
2014-01
期刊：
Nature reviews. Rheumatology
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作者：
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