Wnt/β-catenin and Hedgehog pathways are involved in the inflammatory effect of Interleukin 18 on rat chondrocytes.

Wnt/β-catenin and Hedgehog pathways are involved in the inflammatory effect of Interleukin 18 on rat chondrocytes.
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Wnt/β-catenin 和 Hedgehog 通路参与白细胞介素 18 对大鼠软骨细胞的炎症作用

DOI:
10.18632/oncotarget.20584
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发表时间:
2017-12-15
期刊:
影响因子:
--
通讯作者:
Wu L
Wu L
中科院分区:
其他
文献类型:
--
作者:
Bao J;Ma C;Ran J;Xiong Y;Yan S;Wu L

文献摘要

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探讨白细胞介素18(IL-18)对大鼠软骨细胞的炎症作用以及Wnt/β-catenin和Hedgehog途径、基质降解酶的mRNA和蛋白水平的参与(MMP-2、3、9、13和聚集蛋白聚糖)和软骨细胞特异性蛋白通过qRT-PCR和蛋白质印迹法评估了Wnt/β-连环蛋白和Hedgehog途径(包括β-连环蛋白,免疫印迹法检测GSK-3β、DKK-1、IHH、SHH和Gli-2。Dickkopf-1(DKK-1)和环巴胺作为Wnt/β-catenin和Hedgehog通路的拮抗剂进行通路抑制试验。免疫荧光显微镜观察β-catenin、GSK-3β、Gli-2和Smo的定位和表达。结果显示,IL-18诱导的大鼠软骨细胞炎症反应中,基质降解酶MMP-2、3、9、13和聚集蛋白聚糖在mRNA和蛋白水平上表达上调,软骨细胞特异性蛋白胶原II和聚集蛋白聚糖表达下调,Wnt/β-catenin和Hedgehog通路激活。结论:IL-18的体外致炎作用可能与Wnt/β-catenin和Hedgehog通路有关。
To investigate the inflammatory effect of Interleukin 18 (IL-18) on rat chondrocytes and the involvement of Wnt/β-catenin and Hedgehog pathways, the mRNA and protein level of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and chondrocyte-specific proteins (Collagen II and aggrecan) were evaluated by qRT-PCR and Western blot, and key protein level of Wnt/β-catenin and Hedgehog pathways including β-catenin, GSK-3β, DKK-1, IHH, SHH, and Gli-2 were evaluated by Western blot. Dickkopf-1 (DKK-1) and Cyclopamine were used as antagonist of Wnt/β-catenin and Hedgehog pathways to perform pathway inhibition tests. In addition, location and expression of β-catenin, GSK-3β, Gli-2 and Smo were assessed by Immunofluorescence microscopy. The results showed up-regulation of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and down-regulation of chondrocyte-specific proteins (Collagen II and aggrecan) at both mRNA and protein level and activation of Wnt/β-catenin and Hedgehog pathways in the inflammatory reaction on rat chondrocytes caused by IL-18 treatment was observed. As conclusion, Wnt/β-catenin and Hedgehog pathways are involved in the inflammatory effect of IL-18 in vitro.