Upregulation of Sirt1 by tyrosol suppresses apoptosis and inflammation and modulates extracellular matrix remodeling in interleukin-1β-stimulated human nucleus pulposus cells through activation of PI3K/Akt pathway
Upregulation of Sirt1 by tyrosol suppresses apoptosis and inflammation and modulates extracellular matrix remodeling in interleukin-1β-stimulated human nucleus pulposus cells through activation of PI3K/Akt pathway
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DOI：
10.1016/j.intimp.2020.106904
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发表时间：
2020-11-01
影响因子：
5.6
通讯作者：
Bai, Xiaoliang
中科院分区：
文献类型：
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作者：
Qi, Wei;Ren, Dong;Bai, Xiaoliang
椎间盘退变（IDD）是腰痛的主要发病机制。酪醇是一种多酚类化合物，具有抗氧化、抗细胞凋亡和抗炎作用。在此，我们探讨了酪醇对白细胞介素(IL)-1 β刺激的人髓核细胞（HNPCs） IDD进展的影响及其机制。CCK-8检测细胞活力，流式细胞术检测细胞凋亡。检测肿瘤坏死因子- α (tnf - α)、IL-6、一氧化氮（NO）和前列腺素E2 （PGE2）的产生以评估炎症。采用qRT-PCR检测基质金属蛋白酶（MMPs） （MMP-3/9/13）、II型胶原蛋白、sry相关高迁移率组9 （SOX-9）、聚集蛋白mRNA的表达。western blot检测沉默信息调控因子2同源物1 （Sirtl）、磷酸化蛋白激酶B （p-Akt）、Akt、II型胶原蛋白、SOX-9和聚集蛋白的蛋白水平。结果表明，酪醇可减弱IL-1 β诱导的HNPCs细胞活力降低、细胞凋亡和caspase-3/7活性。在IL-1 β处理的HNPCs中，tnf - α、IL-6、NO和PGE2的产生增加被酪醇处理消除。Tyrosol治疗逆转了IL-1 β诱导的HNPCs中MMP-3、MMP-9和MMP-13的上调，以及II型胶原、SOX-9和聚集蛋白的下调。此外，酪醇处理激活了IL-1 β刺激的HNPCs中磷脂酰肌醇3-激酶(PI3K)/Akt通路。酪醇上调Sirtl， Sirtl沉默抑制HNPCs中Akt磷酸化。Sirtl敲低可减弱酪醇对IL-1 β诱导的HNPCs细胞凋亡、炎症和ECM重塑的影响。综上所述，酪醇上调Sirtl抑制IL-1 β刺激的HNPCs细胞凋亡和炎症，并通过激活PI3K/Akt通路调节ECM重塑。
Intervertebral disc degeneration (IDD) is the major pathogenesis of lower back pain. Tyrosol is a polyphenolic compound that exhibits anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Herein, we explored the effects and mechanisms of tyrosol on IDD progression in interleukin (IL)-1 beta-stimulated human nucleus pulposus cells (HNPCs). Cell viability and apoptosis were detected by CCK-8 and flow cytometry analysis, respectively. The production of tumor necrosis factor-alpha (TNF-alpha), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2) was examined to evaluate inflammation. The mRNA expression of matrix metalloproteinases (MMPs) (MMP-3/9/13), collagen type II, SRY-related high mobility group box 9 (SOX-9), and aggrecan was measured by qRT-PCR. Protein levels of silent information regulator 2 homolog 1 (Sirtl), phosphorylated protein kinase B (p-Akt), Akt, collagen type II, SOX-9, and aggrecan were determined by western blot. Results showed that tyrosol attenuated IL-1 beta-induced viability reduction, apoptosis, and caspase-3/7 activity in HNPCs. The increase in the production of TNF-alpha, IL-6, NO, and PGE2 in IL-1 beta-treated HNPCs was abolished by tyrosol treatment. Tyrosol treatment reversed IL-1 beta-induced upregulation of MMP-3, MMP-9, and MMP-13, and downregulation of collagen II, SOX-9, and aggrecan in HNPCs. Additionally, tyrosol treatment activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in IL-1 beta-stimulated HNPCs. Sirtl was upregulated by tyrosol, and Sirtl silencing inhibited Akt phosphorylation in HNPCs. Sirtl knockdown attenuated the effects of tyrosol on IL-1 beta-induced apoptosis, inflammation, and ECM remodeling in HNPCs. In summary, upregulation of Sirtl by tyrosol suppressed apoptosis and inflammation and regulated ECM remodeling in IL-1 beta-stimulated HNPCs through activation of PI3K/Akt pathway.