Hatane T, Yoshida E, Kawano J, Sugiki M, Onitsuka T, Maruyama M
Department of Physiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-16, Japan.
Biochim Biophys Acta. 1998 Jun 22;1403(2):189-98. doi: 10.1016/s0167-4889(98)00041-x.
This study examines the effects of prostaglandin I2 (PGI2) on urokinase-type plasminogen activator (uPA) production and wound healing by human fibroblasts. Employing fibrin autography, it was found that beraprost sodium, a stable PGI2 analog, enhanced the fibrinolytic activity in media conditioned by human fibroblasts, TIG-3-20 cells. Fibrin zymography, ELISA, and Northern blot analysis confirmed that the enhanced activity was caused by an increase in uPA synthesis and secretion and a decrease in type-1 plasminogen activator inhibitor. While cycloheximide and 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor, suppressed the effect of PGI2, dibutyryl cyclic AMP increased the fibrinolytic activity and uPA mRNA. These findings indicate that PGI2 promotes uPA production in TIG-3-20 cells via direct stimulation of the cyclic AMP intracellular pathway. A similar effect was observed in two other fibroblast cell lines, TIG-7-20 and TIG-7-30. Although PGI2 itself did not affect cellular proliferation, it promoted in vitro repopulation of the denuded area in a wounded monolayer. These observations suggest that PGI2 can stimulate wound healing through the enhanced production of uPA.
本研究探讨前列腺素I2（PGI2）对人成纤维细胞产生尿激酶型纤溶酶原激活物（uPA）及伤口愈合的影响。采用纤维蛋白自显影法发现，稳定的PGI2类似物贝拉普罗斯钠可增强人成纤维细胞TIG - 3 - 20细胞条件培养基中的纤溶活性。纤维蛋白酶谱分析、酶联免疫吸附测定（ELISA）和Northern印迹分析证实，活性增强是由uPA合成与分泌增加以及1型纤溶酶原激活物抑制剂减少所致。虽然放线菌酮和腺苷酸环化酶抑制剂2',5'-二脱氧腺苷可抑制PGI2的作用，但二丁酰环磷腺苷可增加纤溶活性和uPA mRNA。这些发现表明，PGI2通过直接刺激细胞内环磷腺苷（cAMP）途径促进TIG - 3 - 20细胞中uPA的产生。在另外两种成纤维细胞系TIG - 7 - 20和TIG - 7 - 30中也观察到了类似的效应。虽然PGI2本身不影响细胞增殖，但它可促进受伤单层中裸露区域的体外细胞再填充。这些观察结果提示，PGI2可通过增强uPA的产生来刺激伤口愈合。
