Visfatin promotes intervertebral disc degeneration by inducing IL-6 expression through the ERK/JNK/p38 signalling pathways.
Visfatin promotes intervertebral disc degeneration by inducing IL-6 expression through the ERK/JNK/p38 signalling pathways.
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Visfatin通过ERK/JNK/p38信号通路诱导IL-6表达促进椎间盘退变
DOI：
10.1080/21623945.2021.1910155
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发表时间：
2021-12
期刊：
影响因子：
3.3
通讯作者：
Zheng Z
中科院分区：
文献类型：
--
作者：
Cui H;Du X;Liu C;Chen S;Cui H;Liu H;Wang J;Zheng Z
据报道Visfatin可诱导促炎细胞因子的表达。重度椎间盘病变（IVDD）的visfatin表达高于轻度椎间盘病变。然而，visfatin与IVDD之间的直接关系仍有待阐明。本研究旨在阐明IVDD中visfatin的刺激是否由IL-6介导。为探讨visfatin在IVDD中的作用，采用27号针注射visfatin或PBS建立大鼠前盘穿刺模型。结果显示，visfatin组IVDD的组织学形态明显加重。visfatin处理人NP细胞后，胶原和聚集蛋白水平下降，基质金属肽酶3和IL-6水平逐渐升高。visfatin处理后，ERK， JNK和p38磷酸化也迅速增加。与单独用visfatin处理的NP细胞相比，用ERK1/2、JNK和p38抑制剂或靶向p38、ERK和JNK的siRNA预处理的NP细胞显示出IL-6的显著抑制。我们的数据首次证明了visfatin通过JNK/ERK/p38-MAPK信号通路促进NP细胞中IL-6的表达。此外，我们的研究结果表明硬膜外脂肪和visfatin是控制ivdd相关炎症的潜在治疗靶点。
Visfatin reportedly induces the expression of proinflammatory cytokines. Severe grades of intervertebral disc disease (IVDD) exhibit higher expression of visfatin than mild ones. However, the direct relationship between visfatin and IVDD remains to be elucidated. This study aimed to clarify whether stimulation of visfatin in IVDD is mediated by IL-6. To investigate the role of visfatin in IVDD, a rat model of anterior disc puncture was established by injecting visfatin or PBS using a 27-gauge needle. Results revealed an obvious aggravation of the histological morphology of IVDD in the visfatin group. On treating human NP cellswith visfatin, the levels of collagenII and aggrecan decreased and those of matrix metallopeptidase 3 and IL-6 gradually increased. A rapid increase in ERK, JNK, and p38 phosphorylation was also noted after visfatin treatment. Compared to those treated with visfatin alone, NP cells pretreated with ERK1/2, JNK, and p38 inhibitors or siRNA targeting p38, ERK, and JNK exhibited a significant suppression of IL-6. Our data represent the first evidence that visfatin promotes IL-6 expression in NP cells via the JNK/ERK/p38-MAPK signalling pathways. Further, our findings suggest epidural fat and visfatin as potential therapeutic targets for controlling IVDD-associated inflammation.
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影响因子：
7.4
作者：
Noponen-Hietala, N;Virtanen, L;Ala-Kokko, L
通讯作者：
Ala-Kokko, L
影响因子：
5.2
作者：
Khan AN;Jacobsen HE;Khan J;Filippi CG;Levine M;Lehman RA Jr;Riew KD;Lenke LG;Chahine NO
通讯作者：
Chahine NO
DOI：
10.1038/nrrheum.2013.160
发表时间：
2014-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.8
作者：
Segar, Anand H.;Fairbank, Jeremy C. T.;Urban, Jill
通讯作者：
Urban, Jill
影响因子：
3
作者：
Murata, Yasuaki;Rydevik, Bjorn;Olmarker, Kjell
通讯作者：
Olmarker, Kjell