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首页> 外文期刊>Cellular Physiology and Biochemistry >Quantitative characterization of 15-deoxy-Delta(12,14)-prostaglandin J(2) in regulating EGFP-Smad2 translocation in CHO cells through PPAR gamma/TGF beta/Smad2 pathway
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Quantitative characterization of 15-deoxy-Delta(12,14)-prostaglandin J(2) in regulating EGFP-Smad2 translocation in CHO cells through PPAR gamma/TGF beta/Smad2 pathway

机译：定量表征15-脱氧-Delta（12,14）-前列腺素J（2）通过PPAR gamma / TGF beta / Smad2途径调节CHO细胞中的EGFP-Smad2易位

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摘要

Smad2 is an important factor in TGF beta/Smad2 signal transduction pathway with ability for signal propagation, it could translocate from cytoplasm to nucleus after the TGF beta receptor-mediated phosphorylation. 15-deoxy-delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a natural agonist of the peroxisome proliferator-activated receptor gamma (PPAR gamma) is found recently to be able to function in the regulation of Smad2 activity. However, no quantification data have been yet reported, and it still keeps suspenseful whether or not 15d-PGJ(2) could regulate Smad2 activity by depending on PPAR gamma through PPAR gamma/TGF beta/Smad2 pathway. In this work, by analyzing the EGFP-Smad2 location in CHO cells according to the Nucleus Trafficking Analysis Module based on IN Cell Analyzer 1000 platform, TGF beta stimulated EGFP-Smad2 translocation regulated by 15d-PGJ(2) was quantitatively investigated. The results showed that TGF beta could induce EGFP-Smad2 translocation from cytoplasm to nucleus by EC50 of 8.83 pM, and 15d-PGJ(2) could impede the TGF beta-stimulated Smad2 translocation by IC50 of 0.68 mu M. Moreover, GW9662, a PPAR gamma antagonist, could attenuate such a 15d-PGJ(2) inhibitory activity by almost one order of magnitude. This result thereby implies that 15d-PGJ(2) might inhibit Smad2 translocation through PPAR7/TGFP/Smad2 pathway. Further investigation discovered that different from the case for 15d-PGJ(2)' rosiglitazone, another PPAR gamma agonist, could enhance Smad2 translocation to nucleus, suggesting that rosiglitazone and 15d-PGJ(2) might take different modes in the activation of PPAR gamma within the signaling pathway. Copyright. (c) 2006 S. Karger AG, Basel.
机译：Smad2是TGFβ/ Smad2信号转导途径中具有信号传播能力的重要因素，在TGFβ受体介导的磷酸化作用下，它可以从细胞质转移到细胞核。 15-deoxy-delta（12,14）-prostaglandin J（2）（15d-PGJ（2）），一种过氧化物酶体增殖物激活受体γ（PPAR gamma）的天然激动剂，最近被发现能够在Smad2活性的调节。但是，尚未有定量数据报道，并且15d-PGJ（2）是否可以通过PPAR gamma / TGF beta / Smad2途径依赖于PPAR gamma来调节Smad2活性仍然令人怀疑。在这项工作中，通过基于基于IN Cell Analyzer 1000平台的核运输分析模块分析CHO细胞中EGFP-Smad2的位置，定量研究了15d-PGJ（2）调控的TGFβ刺激的EGFP-Smad2易位。结果表明，TGFβ可以通过8.83 pM的EC50诱导EGFP-Smad2从细胞质向核的移位，而15d-PGJ（2）可以通过0.68μM的IC50阻止TGFβ刺激的Smad2的移位。 PPARγ拮抗剂可以使这种15d-PGJ（2）抑制活性减弱近一个数量级。因此，该结果暗示15d-PGJ（2）可能通过PPAR7 / TGFP / Smad2途径抑制Smad2易位。进一步的调查发现，与另一种PPARγ激动剂15d-PGJ（2）的罗格列酮的情况不同，它可以增强Smad2向核的转运，这表明罗格列酮和15d-PGJ（2）在激活PPARγ时可能采取不同的模式。在信号通路内。版权。 （c）2006 S. Karger AG，巴塞尔。

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