Maspin increases extracellular plasminogen activator activity associated with corneal fibroblasts and myofibroblasts.
Maspin increases extracellular plasminogen activator activity associated with corneal fibroblasts and myofibroblasts.
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DOI：
10.1016/j.exer.2011.07.008
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发表时间：
2011-11
影响因子：
3.4
通讯作者：
Twining, Sally S.
中科院分区：
文献类型：
--
作者：
Warejcka, Debra J.;Narayan, Malathi;Twining, Sally S.
关键词：
Maspin是一种细胞迁移抑制剂和细胞与ECM粘附刺激剂，由角膜角膜细胞合成并释放到细胞外基质中。当角膜受伤时，伤口下面的静止基质角膜细胞经历凋亡，并且与该凋亡区域相邻的细胞转化为成纤维细胞或肌成纤维细胞。本研究探讨了细胞外maspin对角膜基质细胞损伤后纤溶酶原-纤溶酶原激活物系统的影响。用r-maspin处理角膜成纤维细胞和肌成纤维细胞增加细胞外而非细胞相关的组织型纤溶酶原激活物（tPA）、尿型纤溶酶原激活物（uPA）或纤溶酶原激活物抑制剂-1（派-1）。尽管派-1的细胞外增加，maspin治疗的净效应是纤溶酶原激活的增加。在生理水平，maspin没有改变uPA或tPA mRNA水平，在这些细胞。原型和活性uPA的增加是由于在maspin存在下肌成纤维细胞而非成纤维细胞的清除率降低。原和活性tPA的清除率在成纤维细胞中是正常的，表明这两种细胞类型中这些同源酶增加的机制不同。通过maspin处理的角膜基质成纤维细胞和肌成纤维细胞增加纤溶酶的产生，导致纤溶酶原转化为活性纤溶酶降解产物和血管抑素样分子。该研究表明，细胞外maspin在1-4小时的短时间尺度上增加了由角膜成纤维细胞和肌成纤维细胞释放的前和活性uPA和tPA，但是到24小时，与没有maspin产生的水平相比没有增加。纤溶酶原激活物活性的增强增加了纤溶酶激活和血管抑素的产生。这进一步表明maspin对uPA和tPA水平的影响是细胞类型依赖性的。
Maspin, an inhibitor of cell migration and a stimulator of adhesion of cells to the ECM, is synthesized and released by corneal keratocytes into the extracellular matrix. When the cornea is wounded, the quiescent stromal keratocytes underlying the wound undergo apoptosis and cells adjacent to this apoptotic area convert to fibroblasts or myofibroblasts. This study explores the effect of extracellular maspin on the plasminogen-plasminogen activator system of corneal stromal cells following wounding. Treatment of corneal fibroblasts and myofibroblasts with r-maspin increased extracellular but not cell-associated tissue-type plasminogen activator (tPA), urinary-type plasminogen activator (uPA) or plasminogen activator inhibitor-1 (PAI-1). Despite the extracellular increase in PAI-1, the net effect of maspin treatment was an increase in plasminogen activation. At physiological levels, maspin did not alter uPA or tPA mRNA levels, in these cells. The increase in pro and active uPA was due to decreased clearance in the presence of maspin for myofibroblasts but not for fibroblasts. The clearance of pro and active tPA was normal in fibroblasts indicating different mechanisms for the increase of these homologous enzymes in the two cell types. Increased generation of plasmin by maspin treated corneal stromal fibroblasts and myofibroblasts led to conversion of plasminogen to active plasmin degradation products and angiostatin-like molecules. This study suggests that extracellular maspin increased pro and active uPA and tPA released by corneal fibroblasts and myofibroblasts on the short time scale of 1–4 hours, but by 24 hrs there was no increase over the levels produced without maspin. This augmentation of plasminogen activator activity increases plasmin activation and angiostatin generation. It further indicates that the effect of maspin on uPA and tPA levels is cell type dependent.
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