Suppr超能文献

纤溶酶原激活物抑制剂-1的发育性表达与血小板生成素依赖性巨核细胞分化相关。

Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryocytic differentiation.

作者信息

Madoiwa S, Komatsu N, Mimuro J, Kimura K, Matsuda M, Sakata Y

机构信息

Division of Hemostasis and Thrombosis, Institute of Hematology, Division of Hematology, Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.

出版信息

Blood. 1999 Jul 15;94(2):475-82.

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is present in the platelet alpha-granule and is released on activation. However, there is some debate as to whether the megakaryocyte and platelet synthesize PAI-1, take it up from plasma, or both. We examined the expression of PAI-1 in differentiating megakaryocytic progenitor cells (UT-7) and in CD34(+)/CD41(-) cells from cord blood. UT-7 cells differentiated with thrombopoietin (TPO) resembled megakaryocytes (UT-7/TPO) with respect to morphology, ploidy, and the expression of glycoprotein IIb-IIIa. PAI-1 messenger RNA (mRNA) expression was upregulated and PAI-1 protein synthesized in the UT-7/TPO cells accumulated in the cytoplasm without being released spontaneously. In contrast, erythropoietin (EPO)-stimulated UT-7 cells (UT-7/EPO) did not express PAI-1 mRNA after stimulation with TPO because they do not have endogenous c-Mpl. After cotransfection with human wild-type c-mpl, the cells (UT-7/EPO-MPL) responded to phorbol 12-myristate 13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) with enhanced PAI-1 mRNA expression within 24 to 48 hours. However, induction of PAI-1 mRNA in UT-7/EPO-MPL cells by TPO required at least 14-days stimulation. UT-7/EPO cells expressing c-Mpl changed their morphology and the other characteristics similar to the UT-7/TPO cells. TPO also differentiated human cord blood CD34(+)/CD41(-) cells to CD34(-)/CD41(+) cells, generated morphologically mature megakaryocytes, and induced the expression of PAI-1 mRNA. These results suggest that both PAI-1 mRNA and de novo PAI-1 protein synthesis is induced after differentiation of immature progenitor cells into megakaryocytes by TPO.

摘要

纤溶酶原激活物抑制剂-1(PAI-1)存在于血小板α颗粒中,并在激活时释放。然而,关于巨核细胞和血小板是合成PAI-1、从血浆中摄取PAI-1还是两者兼而有之,存在一些争议。我们检测了PAI-1在分化中的巨核细胞祖细胞(UT-7)和脐带血CD34(+)/CD41(-)细胞中的表达。用血小板生成素(TPO)诱导分化的UT-7细胞(UT-7/TPO)在形态、倍性和糖蛋白IIb-IIIa的表达方面类似于巨核细胞。UT-7/TPO细胞中PAI-1信使核糖核酸(mRNA)表达上调,合成的PAI-1蛋白积聚在细胞质中,不会自发释放。相反,促红细胞生成素(EPO)刺激的UT-7细胞(UT-7/EPO)在用TPO刺激后不表达PAI-1 mRNA,因为它们没有内源性c-Mpl。与人野生型c-mpl共转染后,这些细胞(UT-7/EPO-MPL)在24至48小时内对佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)反应,PAI-1 mRNA表达增强。然而,TPO诱导UT-7/EPO-MPL细胞中PAI-1 mRNA至少需要14天的刺激。表达c-Mpl的UT-7/EPO细胞改变了形态和其他特征,类似于UT-7/TPO细胞。TPO还将人脐带血CD34(+)/CD41(-)细胞分化为CD34(-)/CD41(+)细胞,生成形态成熟的巨核细胞,并诱导PAI-1 mRNA的表达。这些结果表明,未成熟祖细胞经TPO分化为巨核细胞后,PAI-1 mRNA和从头合成的PAI-1蛋白均被诱导。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验