TGF-β Induces Up-Regulation of Chondroitin Sulfate Synthase 1 (CHSY1) in Nucleus Pulposus Cells Through MAPK Signaling
TGF-β Induces Up-Regulation of Chondroitin Sulfate Synthase 1 (CHSY1) in Nucleus Pulposus Cells Through MAPK Signaling
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TGF-β 通过 MAPK 信号传导诱导髓核细胞中硫酸软骨素合酶 1 (CHSY1) 的上调
DOI：
10.1159/000430396
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Yuan, Wen
中科院分区：
文献类型：
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作者：
Hu, Bo;Shi, Changgui;Yuan, Wen
背景/目的：硫酸软骨素合成酶1 （CHSY1）是一种糖基转移酶，参与软骨素和硫酸皮脂糖胺聚糖（GAG）的生物合成。tgf - β可刺激髓核细胞产生硫酸酸化GAG；然而，人们对其潜在机制知之甚少。方法：采用实时荧光定量PCR和Western blot检测tgf - β处理大鼠髓核中CHSY1的表达。通过慢病毒敲低来确定tgf - β的下游效应物，并测量c-Jun和Sp1对tgf - β介导的CHSY1启动子活性和CHSY1表达的影响。结果：tgf - β通过激活典型Smad信号通路部分增加髓核CHSY1表达和启动子活性。c-Jun和Sp1基因的下调降低了CHSY1启动子活性、CHSY1的表达和tgf - β诱导的sGAG积累。此外，我们发现tgf - β诱导的CHSY1表达是通过激活MAPK信号通路介导的。此外，我们发现沉默CHSY1可减少tgf - β诱导的髓核细胞中sGAG的积累。结论：tgf - β通过激活MAPK信号通路诱导髓核中CHSY1的表达。巴塞尔S. Karger股份有限公司版权所有
Background/Aims: Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-beta can stimulate sulfated GAG production in nucleus pulposus cells; however, the underlying mechanisms are poorly understood. Methods: CHSY1 expression was examined in rat nucleus pulposus treated with TGF-beta using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-beta and to measure the effect of c-Jun and Sp1 on TGF-beta mediated CHSY1 promoter activity and CHSY1 expression. Results: TGF-beta increased CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway. Knockdown of c-Jun and Sp1 decreased CHSY1 promoter activity, CHSY1 expression and sGAG accumulation induced by TGF-beta. Furthermore, we found that TGF-beta-induced expression of CHSY1 was mediated through the activation of MAPK signaling. Moreover, we showed that silencing CHSY1 decreased sGAG accumulation in nucleus pulposus cells induced by TGF-beta. Conclusion: Our results suggest that TGF-beta induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling. Copyright (C) 2015 S. Karger AG, Basel