PMID- 26946533 OWN - NLM STAT- MEDLINE DCOM- 20170605 LR - 20220321 IS - 1535-3699 (Electronic) IS - 1535-3702 (Print) IS - 1535-3699 (Linking) VI - 241 IP - 8 DP - 2016 Apr TI - Resveratrol attenuated TNF-alpha-induced MMP-3 expression in human nucleus pulposus cells by activating autophagy via AMPK/SIRT1 signaling pathway. PG - 848-53 LID - 10.1177/1535370216637940 [doi] AB - 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. CI - (c) 2016 by the Society for Experimental Biology and Medicine. FAU - Wang, Xiao-Hu AU - Wang XH AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Zhu, Lei AU - Zhu L AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Hong, Xin AU - Hong X AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Wang, Yun-Tao AU - Wang YT AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Wang, Feng AU - Wang F AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Bao, Jun-Ping AU - Bao JP AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Xie, Xin-Hui AU - Xie XH AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Liu, Lei AU - Liu L AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. FAU - Wu, Xiao-Tao AU - Wu XT AD - Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China wuxiaotao@medmail.com.cn. LA - eng PT - Journal Article DEP - 20160304 PL - Switzerland TA - Exp Biol Med (Maywood) JT - Experimental biology and medicine (Maywood, N.J.) JID - 100973463 RN - 0 (Stilbenes) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) RN - Q369O8926L (Resveratrol) SB - IM MH - AMP-Activated Protein Kinases/antagonists & inhibitors/*physiology MH - Autophagy/*drug effects/physiology MH - Blotting, Western MH - Cells, Cultured MH - Humans MH - Matrix Metalloproteinase 3/*metabolism MH - Nucleus Pulposus/drug effects/*metabolism MH - Real-Time Polymerase Chain Reaction MH - Resveratrol MH - Signal Transduction/drug effects/*physiology MH - Sirtuin 1/antagonists & inhibitors/*physiology MH - Stilbenes/*pharmacology MH - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*pharmacology PMC - PMC4950401 OTO - NOTNLM OT - AMPK OT - MMP-3 OT - Resveratrol OT - SIRT1 OT - TNF-alpha OT - autophagy OT - nucleus pulposus cell EDAT- 2016/03/08 06:00 MHDA- 2017/06/06 06:00 PMCR- 2016/10/01 CRDT- 2016/03/07 06:00 PHST- 2015/12/06 00:00 [received] PHST- 2016/02/05 00:00 [accepted] PHST- 2016/03/07 06:00 [entrez] PHST- 2016/03/08 06:00 [pubmed] PHST- 2017/06/06 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - 1535370216637940 [pii] AID - 10.1177_1535370216637940 [pii] AID - 10.1177/1535370216637940 [doi] PST - ppublish SO - Exp Biol Med (Maywood). 2016 Apr;241(8):848-53. doi: 10.1177/1535370216637940. Epub 2016 Mar 4.