Aucubin inhibits IL‐1β‐ or TNF‐α‐induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR‐140‐5p/CREB1 axis

2019 ◽  
Vol 234 (8) ◽  
pp. 13639-13648 ◽  
Author(s):  
Shaofeng Yang ◽  
Linghui Li ◽  
Liguo Zhu ◽  
Chao Zhang ◽  
Zhaoyong Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation ◽  
Tnf Α

scholarly journals LncRNA NEAT1 promotes nucleus pulposus cell matrix degradation through regulating Nrf2/ARE axis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Cheng Li ◽  
Xinjian Ma ◽  
Chenfei Ni ◽  
Jingyan Xu ◽  
Yinfei Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Matrix Degradation ◽  
Nucleus Pulposus Cells ◽  
Tnf Α ◽  
Healthy Control ◽  
Nrf2 Activator ◽  
Lncrna Neat1 ◽  
Nrf2 Expression

Abstract Background This study aimed to assess the role and mechanism of lncRNA NEAT1 in intervertebral disc degeneration (IVD). Methods LncRNA profile (GSE56081) between IVD and healthy control was downloaded from the Gene Expression Omnibus (GEO) database and analyzes differential lncRNA expression. Expression of lncRNA NEAT1 in IVD tissue and TNF-α/IL-1β-stimulated nucleus pulposus cells were further measured by RT-PCR. The lncRNA NEAT1 overexpression plasmids (pcDNA-NEAT1) were constructed and transfected into nucleus pulposus cells. Catabolic biomarkers (MMP-3 and MMP-13), anabolic biomarkers (Col II and Aggrecan) and Nrf2 expression were further measured. To further investigate the function of Nrf2, nucleus pulposus cells were pretreated with or without 25 μM tert-Butylhydroquinone (TBHQ), a Nrf2 activator, for 18 h and subsequently cotreated with pcDNA-NEAT1. Results A total of 1432 lncRNAs were differentially expressed in GSE56081. Bioinformatic analysis found that these lncRNAs mainly enriched in Nrf2/ARE signaling pathway. LncRNA NEAT1 was highly expressed in IVD tissues than that of healthy control. Moreover, TNF-α/IL-1β induced a time- and dose-dependent increase in the mRNA expression of lncRNA NEAT1 in the nucleus pulposus cells. Overexpression of lncRNA NEAT1 abates promotes nucleus pulposus cells proliferation but induces matrix degradation. Meanwhile, nucleus and cytoplasm Nrf2 expression was significantly down-regulated by lncRNA NEAT1 upregulation. Nrf2 activator (TBHQ) could partially reverse the inhibitory effects of overexpression of lncRNA NEAT1 on matrix degradation. Conclusion Collectively, our data unveiled the lncRNA NEAT1 promotes matrix degradation by regulating Nrf2/ARE signaling pathway, suggesting a potential therapeutic for IVD in the future.

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