Enhanced production of plasminogen activator activity in human and murine keratinocytes by transforming growth factor-beta 1.
Enhanced production of plasminogen activator activity in human and murine keratinocytes by transforming growth factor-beta 1.
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通过转化生长因子-β 1 增强人和鼠角质形成细胞中纤溶酶原激活剂活性的产生。
DOI：
10.1111/1523-1747.ep12616826
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
K. Koli
中科院分区：
文献类型：
--
作者：
J. Keski‐oja;K. Koli
转化生长因子-β（TGF-β）是已知最有效的角质形成细胞生长抑制剂。细胞周蛋白水解活性通常在增殖和恶性细胞中较高，而在静息或生长停滞细胞中降低。因此，我们分析了TGF β 1对正常人角质形成细胞和小鼠角质形成细胞系在无血清条件下产生纤溶酶原激活物活性的影响。采用琼脂中酪蛋白溶解和酶谱分析、免疫印迹和纤溶酶原激活物（PA）和PA抑制剂-1（派-1）的北方杂交分析，分析培养基的纤溶酶原激活物活性。在凝胶的荧光图中观察到放射性标记的多肽的改变。发现与人表皮样癌细胞中一样，皮摩尔浓度的TGF β 1（0.2-20 ng/ml）增强了两种角质形成细胞系统中的总纤溶酶原激活物活性。培养基的酶谱和免疫印迹分析表明，激活剂是尿激酶型（u-PA）。培养基的免疫沉淀和伴刀豆球蛋白A亲和层析表明细胞也开始产生派-1。角质形成细胞的细胞周基质制备物的分析表明派-1沉积到细胞周空间。显然，由于u-PA活性升高，在TGF β 1处理的细胞中派-1比对照培养物更快地从细胞外基质中去除。人角质形成细胞的北方杂交分析表明，TGF β 1迅速升高u-PA和派-1 mRNA水平。时间诱导曲线的比较表明，u-PA的mRNA增加更缓慢，但更持久的派-1。放线菌素D抑制u-PA和派-1 mRNA的诱导，表明诱导是由于转录增加。结果表明，增强的纤溶酶原激活剂活性也可以与非恶性细胞如培养的人或鼠角质形成细胞的生长抑制有关。
Transforming growth factor-beta (TGF beta) is the most potent known inhibitor of keratinocyte growth. Pericellular proteolytic activity is usually high in proliferating and malignant cells and decreased in resting or growth-arrested cells. We have therefore analyzed the effects of TGF beta 1 on the production of plasminogen activator activity by normal human keratinocytes and a mouse keratinocyte cell line under serum-free conditions. The plasminogen activator activity of the culture medium was analyzed using caseinolysis-in-agar and zymography assays, immunoblotting, and Northern hybridization analysis for the plasminogen activators (PA) and PA inhibitor-1 (PAI-1). Alterations of radiolabeled polypeptides were observed in fluorograms of gels. It was found that like in human epidermoid carcinoma cells picomolar concentrations of TGF beta 1 (0.2-20 ng/ml) enhanced total plasminogen activator activity in both keratinocyte cell systems. Zymographic and immunoblotting analyses of the medium indicated that the activator was of the urokinase type (u-PA). Immunoprecipitation and Concanavalin A affinity chromatography of the culture medium indicated that the cells also started to produce PAI-1. Analysis of the pericellular matrix preparations of the keratinocytes showed that PAI-1 is deposited to the pericellular space. Evidently due to elevated u-PA activity PAI-1 was removed from the extracellular matrix more rapidly in TGF beta 1-treated cells than from control cultures. Northern hybridization analysis of human keratinocytes showed that TGF beta 1 rapidly elevated both u-PA and PAI-1 mRNA levels. Comparison of the temporal induction profiles indicated that the mRNA for u-PA increased more slowly but was more persistent than that of PAI-1. Actinomycin D inhibited the induction of both u-PA and PAI-1 mRNA, suggesting that the induction was due to increased transcription. The results suggest that enhanced plasminogen activator activity can be associated with growth inhibition also in nonmalignant cells like cultured human or murine keratinocytes.
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DOI：
--
发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Ignotz;J. Massagué
通讯作者：
R. Ignotz;J. Massagué
DOI：
10.1016/s0021-9258(18)69042-8
发表时间：
1988-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Keski‐oja;R. Raghow;M. Sawdey;D. Loskutoff;A. Postlethwaite;A. Kang;H. Moses
通讯作者：
J. Keski‐oja;R. Raghow;M. Sawdey;D. Loskutoff;A. Postlethwaite;A. Kang;H. Moses
DOI：
10.1073/pnas.83.18.6776
发表时间：
1986-09-01
影响因子：
11.1
作者：
NY, T;SAWDEY, M;LOSKUTOFF, DJ
通讯作者：
LOSKUTOFF, DJ
转化生长因子-β 在体外调节人角质形成细胞中纤溶酶原激活剂活性和纤溶酶原激活剂抑制剂 1 型表达。
DOI：
10.1111/1523-1747.ep12505603
发表时间：
1990
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Wikner,NE;Elder,JT;Persichitte,KA;Mink,P;Clark,RA
通讯作者：
Clark,RA
影响因子：
6.5
作者：
CLARK, RAF;LANIGAN, JM;COLVIN, RB
通讯作者：
COLVIN, RB