Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes
Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes
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DOI：
10.1161/01.atv.20.6.1682
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发表时间：
2000-06-01
影响因子：
8.7
通讯作者：
Hauner, H
中科院分区：
文献类型：
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作者：
Birgel, M;Gottschling-Zeller, H;Hauner, H
纤溶酶原激活物抑制剂-1（PAI-1）水平升高是肥胖的特征，并与血栓栓塞并发症的风险增加有关。派-1是近年来发现的由脂肪细胞表达和分泌的蛋白质，但对派-1在脂肪组织中的表达调控机制尚不清楚。因此，我们研究了存在于脂肪组织中的所选细胞因子对原代培养的体外分化的皮下人脂肪细胞中派-1的表达和分泌的影响。转化生长因子-α（TGF-β 1）以剂量和时间依赖性方式增加PAI-1分泌。400 pmol/L TGF-β 1暴露6小时后，派-1蛋白增加3.2倍，PAI-I mRNA增加1.9倍。这种作用可能是由TGF-β 1 2型和3型受体介导的，发现它们在培养的人脂肪细胞中表达。此外，TNF-α和白细胞介素-1 β（IL-1 β）也对派-1释放产生刺激作用，并增加派-1 mRNA水平。通过半定量逆转录-聚合酶链反应技术评估，TGF-β 1 mRNA通过人前脂肪细胞的分化表达，并通过TNF-α和IL-β适度上调。总之，我们的结果清楚地表明，TGF-β是皮下人脂肪细胞中派-1产生的有效诱导剂。此外，数据表明TNF-α和IL-1 β也对派-1蛋白分泌具有刺激作用，并可能导致肥胖症中观察到的派-1水平升高。
Elevated levels of plasminogen activator inhibitor-1 (PAI-I) are characteristic for obesity and are associated with increased risk of thromboembolic complications. PAI-1 recently was reported to be expressed and secreted by human adipocytes, but little is known about regulation of PAI-1 in human adipose tissue. Therefore, we examined the effects of selected cytokines present in adipose tissue on expression and secretion of PAI-1 in in vitro, differentiated subcutaneous human adipocytes in primary culture. Transforming growth factor-alpha (TGF-beta 1) increased PAI-I secretion in a dose- and time-dependent manner. PAI-1 protein increased by 3.2-fold and PAI-I mRNA by 1.9-fold after a 6-hour exposure to 400 pmol/L TGF-beta 1. This effect is probably mediated by TGF-beta 1 type 2 and 3 receptors, which were found to be expressed in cultured human adipocytes. Moreover, TNF-alpha and interkeukin-1 beta (IL-1 beta) also exerted a stimulatory effect on PAI-1 release and increased PAI-1 mRNA levels. As assessed by a semiquantitative reverse transcription-polymerase chain reaction technique, TGF-beta 1 mRNA is expressed by differentiation of human preadipocytes and is moderately upregulated by TNF-alpha and IL-beta, In conclusion, our results clearly indicate that TGF-beta is a potent inducer of PAI-1 production in subcutaneous human adipocytes. In addition, data suggest that TNF-alpha and IL-1 beta also have stimulatory effects on PAI-1 protein secretion and may contribute to the elevated PAI-1 levels observed in obesity.