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首页> 外文期刊>American Journal of Physiology >The inflammatory cytokine oncostatin M induces PAI-1 in human vascular smooth muscle cells in vitro via PI 3-kinase and ERK1/2-dependent pathways.
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The inflammatory cytokine oncostatin M induces PAI-1 in human vascular smooth muscle cells in vitro via PI 3-kinase and ERK1/2-dependent pathways.

机译：炎性细胞因子抑制素M通过PI 3-激酶和ERK1 / 2依赖性途径在体外诱导人血管平滑肌细胞中的PAI-1。

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摘要

Plasminogen activator inhibitor-1 (PAI-1) plays a pivotal role in the regulation of the fibrinolytic system and in the modulation of extracellular proteolysis. Increased PAI-1 was found in atherosclerotic lesions, and high PAI-1 plasma levels were associated with coronary heart disease. Smooth muscle cells (SMC) are a major source of PAI-1 within the vascular wall, and PAI-1 was implicated in SMC migration, proliferation, and apoptosis. We treated human coronary artery SMC (HCASMC) and human aortic SMC (HASMC) with the glycoprotein 130 (gp130) ligands cardiotrophin-1, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), or oncostatin M (OSM). Only OSM increased PAI-1 antigen and activity production significantly in these cells up to 20-fold. OSM upregulated mRNA specific for PAI-1 up to 4.5-fold in these cells. HCASMC and HASMC express gp130, OSM receptor, IL-6 receptor, and LIF receptor. OSM induced extracellular signal-regulated kinase (ERK) 1/2 and Akt phosphorylations in HASMC. A phosphatidylinositol 3-kinase inhibitor and a mitogen-activated protein/extracellular signal-regulated kinase inhibitor reduced Akt and ERK1/2 phosphorylation, respectively, and abolished OSM-induced PAI-1 upregulation. A janus kinase/signal transducer and activator of transcription inhibitor, a p38 mitogen-activated protein kinase inhibitor, or c-Jun NH(2)-terminal kinase inhibitor I did not inhibit the OSM-dependent PAI-1 induction. OSM enhanced proliferation of both HCASMC and HASMC by 77 and 90%, respectively. We hypothesize that, if the effect of OSM on PAI-1 expression in smooth muscle cells is operative in vivo, it could, via modulation of fibrinolysis and extracellular proteolysis, be involved in the development of vascular pathologies such as plaque progression, destabilization and subsequent thrombus formation, and restenosis and neointima formation.
机译：纤溶酶原激活物抑制剂1（PAI-1）在纤维蛋白溶解系统的调节和细胞外蛋白水解的调节中起着关键作用。在动脉粥样硬化病变中发现PAI-1增加，而高PAI-1血浆水平与冠心病有关。平滑肌细胞（SMC）是血管壁内PAI-1的主要来源，PAI-1与SMC迁移，增殖和凋亡有关。我们用糖蛋白130（gp130）配体心肌蛋白1，白介素6（IL-6），白血病抑制因子（LIF）或制瘤素M（OSM）来治疗人冠状动脉SMC（HCASMC）和人主动脉SMC（HASMC） 。在这些细胞中，只有OSM显着提高PAI-1抗原和活性的产生，最多可达20倍。 OSM在这些细胞中上调了对PAI-1特异的mRNA最多4.5倍。 HCASMC和HASMC表达gp130，OSM受体，IL-6受体和LIF受体。 OSM诱导HASMC中的细胞外信号调节激酶（ERK）1/2和Akt磷酸化。磷脂酰肌醇3-激酶抑制剂和有丝分裂原激活的蛋白质/细胞外信号调节激酶抑制剂分别降低了Akt和ERK1 / 2磷酸化，并废除了OSM诱导的PAI-1上调。 janus激酶/信号转导子和转录抑制剂激活剂，p38丝裂原激活的蛋白激酶抑制剂或c-Jun NH（2）-末端激酶抑制剂I不抑制OSM依赖性PAI-1的诱导。 OSM将HCASMC和HASMC的增殖分别提高了77％和90％。我们假设，如果OSM对平滑肌细胞中PAI-1表达的作用在体内起作用，则它可能通过调节纤维蛋白溶解和细胞外蛋白水解作用，参与血管病理的发展，例如斑块进展，不稳定和随后的发展。血栓形成，再狭窄和新内膜形成。

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