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

Wang, Xiaohu; Zhu, Lei; Hong, Xin; Wang, Yuntao; Wang, Feng; Bao, Jun-Ping; Xie, Xinhui; Liu, Lei; Wu, Xiao‐Tao

doi:10.1177/1535370216637940

Cited by 79 publications

(54 citation statements)

References 44 publications

(46 reference statements)

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“…In recent studies, autophagy has been thought to be a protective mechanism under pathological conditions, degrading damaged organelles or proteins . Autophagy has been proven by our group as well as other groups to postpone IDD processes in vitro and in vivo. Xu et al reported that rapamycin‐stimulated autophagy may inhibit intermittent mechanical stress‐induced calcification in cartilage EPCs .…”

Section: Discussionmentioning

confidence: 87%

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Zhang

Lin

Tian

et al. 2018

J Cellular Molecular Medi

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Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose‐dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3‐methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX‐527 suppressed melatonin‐induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1‐autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1‐autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.

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Section: Discussionmentioning

confidence: 87%

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Zhang

Lin

Tian

et al. 2018

J Cellular Molecular Medi

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“…demonstrated that resveratrol induces autophagy by directly inhibiting the mammalian target of rapamycin (mTOR)- Unc-51-like kinase-1 (ULK1) pathway. Other studies suggested that resveratrol attenuated tumor necrosis factor-α (TNF-α)-induced matrix metalloprotease-3 (MMP-3) expression in human nucleus pulposus cells by activating autophagy via the AMPK/SIRT1 signaling pathway34. In addition to intracellular signaling pathways, miRNAs have been shown to play a central role in autophagy regulation1819.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy

Huang

Ding

Chen

et al. 2017

Sci Rep

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Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA-383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucose-induced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR-383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy.

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“…Previous studies have investigated the effects of RSV on human, rat, and bovine NP cells in vitro. RSV suppressed NP cell death as well as senescence and promoted NP cell proliferation through activating silent information regulator 2 ortholog 1 (SIRT1) and PI3K/Akt/caspase-3 pathway [26–32]. SIRT1 is a longevity gene.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

Feng

Yang

Lan

et al. 2017

Oxidative Medicine and Cellular Longevity

262

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Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD.

show abstract

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

Cited by 79 publications

References 44 publications

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

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