Signaling pathways involved in DNA synthesis and migration in response to lysophosphatidic acid and low-density lipoprotein in coronary artery smooth muscle cells
Signaling pathways involved in DNA synthesis and migration in response to lysophosphatidic acid and low-density lipoprotein in coronary artery smooth muscle cells
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DOI：
10.1016/j.vph.2009.01.004
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Okajima, Fumikazu
中科院分区：
文献类型：
--
作者：
Komachi, Mayumi;Damirin, Alatangaole;Okajima, Fumikazu
低密度脂蛋白（LDL）及其脂质成分溶血磷脂酸（LPA）可诱导冠状动脉平滑肌细胞（CASMCs）DNA合成。LPA受体拮抗剂Ki 16425、百日咳毒素、靶向LPA（1）受体的小干扰RNA和有效的钙调磷酸酶抑制剂环孢素A可显著抑制LDL和LPA诱导的DNA合成。据报道，LDL和LPA以对Ki-16425、百日咳毒素和LPA（1）受体特异性小干扰RNA敏感的方式诱导迁移反应。然而，环孢素A在抑制迁移反应方面无效。相反，表皮生长因子（EGF）受体酪氨酸激酶抑制剂显着抑制迁移反应LDL和LPA没有任何显着影响DNA合成。因此，LDL诱导的CASMC中DNA合成和迁移的刺激是由其组分LPA通过LPA（1）受体和G（i/o）-蛋白介导的。Ca 2 +/钙调神经磷酸酶途径和EGF受体的反式激活分别介导LPA（1）受体诱导的DNA合成和迁移。(C)2009 Elsevier Inc. All rights reserved.
Low-density lipoprotein (LDL) and lysophosphatidic acid (LPA), one of the lipid components of lipoprotein, induced the DNA synthesis of coronary artery smooth muscle cells (CASMCs). The LDL- and LPA-induced DNA synthesis was markedly inhibited by the LPA receptor antagonist Ki16425, pertussis toxin, small interfering RNAs targeted for LPA(1) receptors, and a potent calcineurin inhibitor cyclosporine A. It has been reported that LDL and LPA induced a migration response in a manner sensitive to Ki-16425, pertussis toxin, and a LPA(1) receptor-specific small interfering RNA. However, cyclosporine A was ineffective in inhibiting the migration response. Instead, an epidermal growth factor (EGF) receptor tyrosine kinase inhibitor markedly suppressed the migration response to LDL and LPA without having any significant effect on DNA synthesis. Thus, the LDL-induced stimulation of DNA synthesis and migration in CASMCs is mediated by its component LPA through LPA(1) receptors and G(i/o)-proteins. Ca2+/calcineurin pathways and transactivation of EGF receptors mediate LPA(1)-receptor-induced DNA synthesis and migration, respectively. (C) 2009 Elsevier Inc. All rights reserved.