Regulation of tissue-type plasminogen activator and Its Inhibitor (PAI-1) by lipopolysaccharide-induced phagocytosis in a Sertoli cell line

Regulation of tissue-type plasminogen activator and Its Inhibitor (PAI-1) by lipopolysaccharide-induced phagocytosis in a Sertoli cell line
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DOI:
10.1006/excr.1998.4369
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发表时间:
1999-03-15
影响因子:
3.7
通讯作者:
Pointis, G
Pointis, G
中科院分区:
医学3区
文献类型:
--
作者:
Bourdon, V;Defamie, N;Pointis, G

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纤溶酶原激活物(PA)系统被认为在与精子发生相关的蛋白分解事件中发挥重要作用。生精上皮中PA及其主要生理抑制物纤溶酶原激活物抑制物-1(PAI-1)的表达调控机制尚不清楚。在本研究中,我们分析了小鼠支持细胞系(42GPA9)在脂多糖(LPS)刺激下PA和PAI-1的表达,以激活这些细胞的吞噬活性。酶谱分析和tPA转录本的存在证明,在基础条件下培养的永生化Sertoli细胞主要分泌组织型PA(TPA)。在酶谱实验中,还观察到了与PA-PAI-1复合体形成相对应的较大分子量的蛋白水解带。脂多糖刺激永生化Sertoli细胞后,tPA表观分子量增加,PAI-1合成增加。佛波酯TPA类似地刺激Sertoli细胞合成PAI-1,而8-溴-cAMP则没有作用。这些结果首次表明,吞噬作用触发的分子事件与支持细胞中tPA和PAI-1的调节之间存在直接联系。(C)1999年学术出版社。
The plasminogen activator (PA) system is thought to play a major role in the proteolytic events associated with spermatogenesis. The mechanisms controlling the expression of PA and of its major physiological inhibitor, plasminogen activator inhibitor type-1 (PAI-1), in the seminiferous epithelium are still unknown. In the present study we analyzed the expression of PA and PAI-1 in a murine Sertoli cell line (42GPA9) in response to stimulation by lipopolysaccharides (LPS) used to activate the phagocytic activity of these cells. Immortalized Sertoli cells cultured under basal conditions secreted predominantly tissue-type PA (tPA) as demonstrated by zymographic analysis and the presence of tPA transcripts. In zymographic experiments a larger molecular weight proteolytic band corresponding to the formation of PA-PAI-1 complex was also observed. The stimulation of immortalized Sertoli cells by LPS resulted in both alteration of the apparent tPA molecular weight to a higher form and transient increase in PAI-1 biosynthesis. The phorbol ester TPA stimulates similarly PAI-1 synthesis in the Sertoli cell line, while 8-bromo-cAMP has no effect. These results suggest for the first time the existence of a direct linkage between molecular events triggered by phagocytosis and regulation of tPA and PAI-1 in Sertoli cells. (C) 1999 Academic Press.