GROWTH-FACTORS ARE RELEASED BY MECHANICALLY WOUNDED ENDOTHELIAL-CELLS
GROWTH-FACTORS ARE RELEASED BY MECHANICALLY WOUNDED ENDOTHELIAL-CELLS
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DOI：
10.1083/jcb.109.2.811
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发表时间：
1989-08-01
影响因子：
7.8
通讯作者：
DAMORE, PA
中科院分区：
文献类型：
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作者：
MCNEIL, PL;MUTHUKRISHNAN, L;DAMORE, PA
在体内机械损伤和正常磨损的部位可能需要生长因子，这表明机械力对细胞的直接作用可能导致生长因子释放。在37 ℃下从组织培养基质中刮取细胞用于测试这种可能性。我们表明，刮擦在体外紧密地模拟了在体内经受机械力的细胞中观察到的瞬时质膜创伤（McNeil，P.L.，和S.伊藤1989.胃肠病学。96：1238-1248）和此处显示的在正常培养条件下在内皮细胞中发生的瞬时质膜创伤。从培养基质中刮取内皮细胞释放到培养基中，对Swiss 3 T3成纤维细胞具有有效的促生长活性。生长促进活性迅速释放（5分钟内）刮擦后，但随后不降解的内皮细胞至少24小时后。接种后4 h刮取的细胞比接种后4 d或7 d刮取的细胞释放更大量的促生长活性。因此，释放不是由于刮擦诱导的细胞外基质破坏。释放只有部分冷不可逆的，是不相关的刮诱导的细胞死亡的水平，并没有发生当细胞被杀死与代谢毒物。这些结果表明，机械破坏质膜，无论是短暂的或永久的，是必不可少的事件，导致释放。碱性成纤维细胞生长因子样分子，而不是血小板衍生的生长因子似乎是部分负责的生长促进活性。我们的结论是，一个生物相关的释放途径的碱性成纤维细胞生长因子，缺乏信号肽序列转运到内质网的分子，可以直接通过机械诱导的膜破裂的内皮细胞生长在体内和体外。
Growth factors may be required at sites of mechanical injury and normal wear and tear in vivo, suggesting that the direct action of mechanical forces on cells could lead to growth factor release. Scraping of cells from the tissue culture substratum at 37.degree.C was used to test this possibility. We show that scraping closely mimics in vitro both the transient plasma membrane wounds observed in cells subject to mechanical forces in vivo (McNeil, P. L., and S. Ito. 1989. Gastroenterology. 96:1238-1248) and the transient plasma membrane wounds shown here to occur in endothelial cells under normal culturing conditions. Scraping of endothelial cells from the culturing substratum released into the culture medium a potent growth-promoting activity for Swiss 3T3 fibroblasts. Growth-promoting activity was released rapidly (within 5 min) after scraping but was not subsequently degraded by the endothelial cells for at least 24 h thereafter. A greater quantity of growth-promoting activity was released by cells scraped 4 h after plating than by those scraped 4 or 7 d afterwards. Thus release is not due to scraping-induced disruption of extracellular matrix. Release was only partially cold inhibitable, was poorly correlated with the level of cell death induced by scraping, and did not occur when cells were killed with metabolic poisons. These results suggest that mechanical disruption of plasma membrane, either transient or permanent, is the essential event leading to release. A basic fibroblast growth factor-like molecule and not platelet-derived growth factor appears to be partially responsible for the growth-promoting activity. We conclude that one biologically relevant route of release of basic fibroblast growth factor, a molecule which lacks the signal peptide sequence for transport into the endoplasmic reticulum, could be directly through mechanically induced membrane disruptions of endothelial cells growing in vivo and in vitro.