Regulation of CCN2/connective tissue growth factor expression in the nucleus pulposus of the intervertebral disc: role of Smad and activator protein 1 signaling.
Regulation of CCN2/connective tissue growth factor expression in the nucleus pulposus of the intervertebral disc: role of Smad and activator protein 1 signaling.
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DOI：
10.1002/art.27445
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发表时间：
2010-07
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.;Markova, Dessislava;Smith, Harvey E.;Susarla, Bala;Ponnappan, Ravi Kumar;Anderson, D. Greg;Symes, Aviva;Shapiro, Irving M.;Risbud, Makarand V.
探讨转化生长因子β对髓核细胞结缔组织生长因子表达的调节作用。实时荧光定量RT-PCR和Western印迹分析检测髓核CTGF的表达。转染法检测Smad2/3/7和AP1对转化生长因子β介导的结缔组织生长因子启动子活性的影响。CTGF在新生大鼠关节盘中的表达低于骨骼成熟大鼠关节盘。经转化生长因子β处理后，髓核细胞结缔组织生长因子表达增强，启动子活性增强。缺失分析表明，缺少Smad和AP1基序的启动子结构对处理没有反应。分析表明，全长Smad3和Smad3-MH2结构域单独增加了CTGF的活性。当dN-Smad3、siRNA-Smad3、Smad7和Dn-AP1抑制转化生长因子β介导的CTGF启动子的激活时，Smad3和AP1参与了进一步的证据。当Smad3或AP1位点发生突变时，转化生长因子β对CTGF启动子的诱导作用被抑制。我们还观察到，与野生型相比，Smad3基因缺失的小鼠椎间盘中CTGF的表达减少。对人髓核的分析表明，在退变状态下，CTGFmRNA和转化生长因子β表达有增加的趋势。转化生长因子β通过Smad3和AP1在髓核中发挥正调控作用。我们认为CTGF是退变椎间盘有限修复反应的一部分。
To investigate TGFβ regulation of CTGF expression in cells of the nucleus pulposus. Real Time RT-PCR and Western blot analysis was used to measure CTGF expression in the nucleus pulposus. Transfections were used to measure the effect of Smad2/3/7 and AP1on TGFβ mediated CTGF promoter activity. CTGF expression was lower in the neonatal disc compared with the skeletally mature rat disc. An increase in CTGF expression and promoter activity was observed in nucleus pulposus cells after TGFβ treatment. Deletion analysis indicated that promoter constructs lacking smad and AP1 motifs were unresponsive to treatment. Analysis showed that full-length Smad3 and the Smad3-MH2 domain alone increased CTGF activity. Further evidence of Smad3 and AP1 involvement was seen when DN-Smad3, SiRNA-Smad3, smad7 and DN-AP1 suppressed TGFβ mediated activation of the CTGF promoter. When either Smad3 or AP1 sites were mutated, CTGF promoter induction by TGFβ was suppressed. We also observed a decrease in expression of CTGF in discs of Smad3 null mice compared to the wild type. Analysis of human nucleus pulposus indicated a trend of increasing CTGF and TGFβ expression in the degenerate state. TGFβ, through Smad3 and AP1, serves as a positive regulator of CTGF expression in the nucleus pulposus. We propose that CTGF is a part of the limited reparative response of the degenerate disc.
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影响因子：
--
作者：
Erwin, W. Mark;Ashman, Keith;Inman, Robert D.
通讯作者：
Inman, Robert D.
影响因子：
9.8
作者：
Brigstock, David R.
通讯作者：
Brigstock, David R.
影响因子：
10.3
作者：
Chang, Cheng-Chi;Lin, Ming-Tsai;Kuo, Min-Liang
通讯作者：
Kuo, Min-Liang
影响因子：
4.8
作者：
Inoki, I;Shiomi, T;Okada, Y
通讯作者：
Okada, Y
DOI：
10.1016/j.bbrc.2008.05.044
发表时间：
2008-07-25
影响因子：
3.1
作者：
Fujita, Nobuyuki;Imai, Jun-ichi;Miyamoto, Takeshi
通讯作者：
Miyamoto, Takeshi