Resveratrol attenuated TNF-α-induced MMP-3 expression in human nucleus pulposus cells by activating autophagy via AMPK/SIRT1 signaling pathway

被引：76

作者：

Wang, Xiao-Hu ^{[1
]}

Zhu, Lei ^{[1
]}

Hong, Xin ^{[1
]}

Wang, Yun-Tao ^{[1
]}

Wang, Feng ^{[1
]}

Bao, Jun-Ping ^{[1
]}

Xie, Xin-Hui ^{[1
]}

Liu, Lei ^{[1
]}

Wu, Xiao-Tao ^{[1
]}

机构：

[1] Southeast Univ, Sch Med, Zhongda Hosp, Spine Ctr, Nanjing 210009, Jiangsu, Peoples R China

来源：

EXPERIMENTAL BIOLOGY AND MEDICINE | 2016年 / 241卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Resveratrol; TNF-alpha; nucleus pulposus cell; MMP-3; autophagy; SIRT1; AMPK; NECROSIS-FACTOR-ALPHA; LOW-BACK-PAIN; MATRIX METALLOPROTEINASE-3; INTERVERTEBRAL DISC; STROMELYSIN; SIRT1; P38; DEGENERATION; INHIBITION; CYTOKINES;

D O I：

10.1177/1535370216637940

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Resveratrol (RSV) is known to play a role of anti-TNF-alpha in a number of cell types. However, whether RSV modulates the effects of TNF-alpha on human nucleus pulposus (NP) cells is unknown. The purpose of this study is to investigate whether RSV regulates TNF-alpha-induced matrix metalloproteinase-3 (MMP-3) expression. Via quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we found that MMP-3 expression induced by TNF-alpha was inhibited by RSV treatment. Depending on Western blot and qRT-PCR assay, we found that RSV induced autophagy in human NP cells, whereas inhibition of autophagy remarkably abolished the restraining role of RSV in the TNF-alpha-mediated up-regulation of MMP-3. Furthermore, RSV increased SIRT1 expression and SIRT1 knockdown significantly suppressed RSV-induced autophagy in NP cells. RSV also activated AMP-activated protein kinase (AMPK), while inhibition of AMPK notably abolished RSV-induced SIRT1 expression. Our data showed that RSV attenuated TNF-alpha-induced MMP-3 expression in human NP cells by activating autophagy via AMPK/SIRT1 signaling pathway. This new finding suggested that RSV might act as a novel preventive and therapeutic role in intervertebral disc degeneration.

引用

页码：848 / 853

页数：6

共 43 条

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