Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells
Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells
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DOI：
10.1016/s0167-4889(01)00103-3
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发表时间：
2001-05-28
影响因子：
5.1
通讯作者：
Kinsella, BT
中科院分区：
文献类型：
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作者：
Miggin, SM;Kinsella, BT
血栓烷(TX)Az和8-表前列腺素(PG)F-2α都被报道在许多物种中刺激血管平滑肌(SM)的有丝分裂。然而。TXA(2)和8-epiPGF(2α)介导的有丝分裂信号在人血管SM中尚未有详细的研究。因此，我们以人子宫黏膜上皮细胞系为模型，研究了血栓素A受体(TP)介导的人血管平滑肌细胞有丝分裂信号的作用。TP激动剂U46619和8-epiPGF(2α)均可诱导ULTR细胞内细胞外信号调节激酶S和c-jun氨基末端激酶S的激活，并呈时间和浓度依赖性。而TP拮抗剂SQ29548可阻断U46619介导的信号转导，仅部分抑制8-epiPGF(2α)介导的ERK和JNK的激活。U46619和8-epiPGF(2α)诱导的ERK激活分别被蛋白激酶C、PKA和肌醇磷脂3-激酶抑制剂GF109203X、H-和Wortmannin抑制，但不受百日咳毒素的影响。此外，U46619介导的ERK激活涉及表皮生长因子(EGF)受体的反式激活。在人类中，TXA(2)通过两种不同的TP亚型发出信号。在研究TP亚型参与有丝分裂信号的过程中，TPα和TPβ都独立地指导U46619和8-epiPGF(2α)介导的ERK和JNK在人胚胎肾(HEK)293细胞中过度表达单独的TP亚型。然而，与ULTR细胞中的情况相反，SQ29548取消了8-epiPGF(2α)通过TPα和TPβ两种途径在HEK 293细胞中介导的ERK和JNK激活，进一步证明了8-epiPGF(2α)可能通过TPS以外的其他受体在人子宫ULTR细胞中传递信号。(C)2001 Elsevier Science B.V.保留所有权利。
Both thromboxane (TX) Az and 8-epi prostaglandin (PG) F-2 alpha have been reported to stimulate mitogenesis of vascular smooth muscle (SM) in a number of species. However. TXA(2) and 8-epiPGF(2 alpha) mediated mitogenic signalling has not been studied in detail in human vascular SM. Thus, using the human uterine ULTR cell line as a model, we investigated TXA-receptor (TP) mediated mitogenic signalling in cultured human vascular SMCs. Both the TP agonist U46619 and 8-epiPGF(2 alpha) elicited time and concentration dependent activation of the extracellular signal regulated kinase (ERK)s and c-Jun N-terminal kinase (JNK)s in ULTR cells. Whereas the TP antagonist SQ29548 abolished U46619 mediated signalling, it only partially inhibited 8-epiPGF(2 alpha) mediated ERK and JNK activation in ULTR cells. Both U46619 and 8-epiPGF(2 alpha) induced ERK activations were inhibited by the protein kinase (PK) C, PKA and phosphoinositide 3-kinase inhibitors GF109203X, H-89 and wortmannin, respectively, but were unaffected by pertussis toxin. In addition, U46619 mediated ERK activation in ULTR cells involves transactivation of the epidermal growth factor (EGF) receptor. In humans, TXA(2) signals through two distinct TP isoforms. In investigating the involvement of the TP isoforms in mitogenic signalling, both TP alpha and TP beta independently directed U46619 and 8-epiPGF(2 alpha) mediated ERK and JNK activation in human embryonic kidney (HEK) 293 cells over-expressing the individual TP isoforms. However, in contrast to that which occurred in ULTR cells, SQ29548 abolished 8-epiPGF(2 alpha) mediated ERK and JNK activation through both TP alpha and TP beta in HEK 293 cells providing further evidence that 8-epiPGF(2 alpha) may signal through alternative receptors, in addition to the TPs, in human uterine ULTR cells. (C) 2001 Elsevier Science B.V. All rights reserved.