Transforming growth factor β controls CCN3 expression in nucleus pulposus cells of the intervertebral disc.
Transforming growth factor β controls CCN3 expression in nucleus pulposus cells of the intervertebral disc.
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转化生长因子β控制椎间盘核细胞中的CCN3表达。
DOI：
10.1002/art.30468
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发表时间：
2011-10
影响因子：
--
通讯作者：
Risbud, Makarand V.
中科院分区：
文献类型：
--
作者：
Tran, Cassie M.;Smith, Harvey E.;Symes, Aviva;Rittie, Laure;Perbal, Bernard;Shapiro, Irving M.;Risbud, Makarand V.
目的：探讨TGFβ对髓核细胞CCN3表达的调控作用。采用Real Time RT-PCR和Western blot检测髓核中CCN3的表达。转染检测Smad3、MAPKs和AP1对TGFβ介导的CCN3启动子活性的影响。通过慢病毒敲低Smad3来评估Smad3在CCN3表达中的作用。CCN3在胚胎和成人椎间盘中均有表达。TGFβ在髓核细胞中降低CCN3的表达并抑制其启动子活性。DN-Smad3、Smad3-siRNA或DN-AP1对tgf - β抑制CCN3启动子活性的影响较小。然而，p38和ERK抑制剂阻断了TGFβ对CCN3的抑制，表明这些信号通路参与了调控。有趣的是，在缺乏TGFβ的情况下，Smad3的过表达增加了CCN3启动子的活性。我们验证了Smad3在Smad3缺失小鼠和慢病毒shSmad3转导的髓核细胞中控制CCN3表达的作用。在功能方面，rCCN3治疗显示出剂量依赖性的髓核细胞增殖减少。此外，CCN3处理的细胞显示aggrecan、versican、CCN2以及I型胶原的表达降低。TGFβ对髓核细胞中CCN2和CCN3表达的相反作用以及CCN3对CCN2的抑制进一步证实了这些CCN蛋白形成相互作用的三联体，可能对维持细胞外基质稳态和细胞数量很重要。
To investigate TGFβ regulation of CCN3 expression in cells of the nucleus pulposus. Real Time RT-PCR and Western blot analysis was used to measure CCN3 expression in the nucleus pulposus. Transfections were used to measure the effect of Smad3, MAPKs and AP1 on TGFβ mediated CCN3 promoter activity. Lentiviral knock down of Smad3 was performed to asses the role of Smad3 in CCN3 expression. CCN3 was expressed in embryonic and adult intervertebral discs. TGFβ decreased CCN3 expression and suppressed its promoter activity in nucleus pulposus cells. DN-Smad3, Smad3-siRNA or DN-AP1 had little effect on TGFβ suppression of CCN3 promoter activity. However, p38 and ERK inhibitors blocked suppression of CCN3 by TGFβ, suggesting involvement of these signaling pathways in the regulation. Interestingly, overexpression of Smad3, in absence of TGFβ increased CCN3 promoter activity. We validated the role of Smad3 in controlling CCN3 expression in Smad3 null mice and in nucleus pulposus cells transduced with lentiviral shSmad3. In terms of function, treatment with rCCN3 showed a dose dependent decrease in proliferation of nucleus pulposus cells. Moreover, CCN3 treated cells shows a decrease in aggrecan, versican, CCN2 as well as collagen type I expression. The opposing effect of TGFβ on CCN2 and CCN3 expression and suppression of CCN2 by CCN3 in nucleus pulposus cells furthers the paradigm that these CCN proteins form an interacting triad, possibly important in maintaining extracellular matrix homeostasis and cell number.
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影响因子：
6.2
作者：
Kawaki, Harumi;Kubota, Satoshi;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu
影响因子：
1.6
作者：
Lee, Yong-Jik;Kong, Min-Ho;Heo, Su-Halk
通讯作者：
Heo, Su-Halk
影响因子：
--
作者：
Tran, Cassie M.;Markova, Dessislava;Smith, Harvey E.;Susarla, Bala;Ponnappan, Ravi Kumar;Anderson, D. Greg;Symes, Aviva;Shapiro, Irving M.;Risbud, Makarand V.
通讯作者：
Risbud, Makarand V.
影响因子：
4.1
作者：
Aoyama, Eriko;Hattori, Takako;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu
DOI：
10.1186/1478-811x-2-9
发表时间：
2004-09-10
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Kyurkchiev, Stanimir;Yeger, Herman;Perbal, Bernard
通讯作者：
Perbal, Bernard