Suppression of PKG by PDGF or nitric oxide in differentiated aortic smooth muscle cells: obligatory role of protein tyrosine phosphatase 1B.
Suppression of PKG by PDGF or nitric oxide in differentiated aortic smooth muscle cells: obligatory role of protein tyrosine phosphatase 1B.
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PDGF 或一氧化氮在分化的主动脉平滑肌细胞中抑制 PKG：蛋白酪氨酸磷酸酶 1B 的必然作用。
DOI：
10.1152/ajpheart.00225.2010
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Hassid,Aviv
中科院分区：
文献类型：
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作者：
Zhuang,Daming;Balani,Poonam;Pu,Qinghua;Thakran,Shalini;Hassid,Aviv
PDGF诱导大鼠主动脉平滑肌细胞蛋白酪氨酸磷酸酶1B表达上调。PTP1B反过来又降低了几种生长因子受体的功能，从而完成了一个负反馈循环。已有研究报道，作为血管平滑肌细胞去分化过程的一部分，PDGF可诱导PKG表达下调。另有研究报道，慢性一氧化氮(NO)处理也可诱导PKG表达下调。在本研究中，我们验证了一种假设，即PDGF或NO下调分化的大鼠主动脉平滑肌细胞中PKG的表达可归因于PTP1B的上调。我们发现，经PDGF或NO处理后，PTP1B水平上调。PTP1B过表达导致PKG mRNA和蛋白水平显著下调，而针对PTP1B的显性负性PTP1B或短干扰RNA的表达阻断了PDGF或NO降低PKG水平的能力。我们的结论是，PDGF或NO上调PTP1B既是必要的，也是充分的，可以通过影响PKG的mRNA水平来诱导PKG的下调。
Treatment of aortic smooth muscle cells with PDGF induces the upregulation of protein tyrosine phosphatase 1B (PTP1B). PTP1B, in turn, decreases the function of several growth factor receptors, thus completing a negative feedback loop. Studies have reported that PDGF induces the downregulation of PKG as part of a repertoire of dedifferentiation of vascular smooth muscle cells. Other studies have reported that chronic nitric oxide (NO) treatment also induces the downregulation of PKG. In the present study, we tested the hypothesis that the downregulation of PKG by PDGF or NO in differentiated rat aortic smooth muscle cells can be attributed to the upregulation of PTP1B. We found that treatment with PDGF or NO induced an upregulation of PTP1B levels. Overexpression of PTP1B induced a marked downregulation of PKG mRNA and protein levels, whereas the expression of dominant negative PTP1B or short interfering RNA directed against PTP1B blocked the capacity of PDGF or NO to decrease PKG levels. We conclude that the upregulation of PTP1B by PDGF or NO is both necessary and sufficient to induce the downregulation of PKG via an effect on PKG mRNA levels.