Extracellular matrix contraction by choroidal fibroblasts: inhibition by staurosporine.

Extracellular matrix contraction by choroidal fibroblasts: inhibition by staurosporine.
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DOI:
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发表时间:
1994-02
影响因子:
4.4
通讯作者:
C. Guidry;C. Hardwick
C. Guidry;C. Hardwick
中科院分区:
医学2区
文献类型:
--
作者:
C. Guidry;C. Hardwick

文献摘要

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目的研究一种广谱激酶抑制剂作为一种中和收缩促进剂对眼细胞影响的手段的潜力。方法采用脉络膜成纤维细胞体外细胞外基质收缩实验,对一种广谱激酶抑制剂的抑制作用进行了检测和表征。结果司陶孢素能有效抑制脉络膜成纤维细胞对胶原基质的收缩。staurosporine的抑制作用起效快,去除抑制剂后可逆。当用血清、转化生长因子β 1、转化生长因子β 2、血小板衍生生长因子和内皮素-1刺激成纤维细胞时,观察到抑制作用。我们还观察到,与转化生长因子相比,血小板来源的生长因子和内皮素-1仅能刺激适度的基质收缩。结论:一种广谱激酶抑制剂可以调节细胞对基质的收缩,正如在牵引力的形成过程中观察到的那样。脉络膜成纤维细胞对血小板源性生长因子和内皮素-1的边际收缩反应都是真皮成纤维细胞收缩的有效促进剂,这表明这两种细胞类型对生长因子的反应存在实质性差异。
PURPOSE To examine the potential of a broad-spectrum kinase inhibitor as a means of neutralizing the effects of contraction promoters on ocular cells. METHODS The inhibitory effects of a broad-spectrum kinase inhibitor were examined and characterized using an in vitro assay of extracellular matrix contraction by choroidal fibroblasts. RESULTS Staurosporine effectively inhibited collagen matrix contraction by choroidal fibroblasts. The inhibitory effects of staurosporine were rapid in onset and reversible upon removal of the inhibitor. Inhibition was observed when fibroblasts were stimulated with serum, transforming growth factor beta 1, transforming growth factor beta 2, platelet-derived growth factor, and endothelin-1. We also observed that platelet-derived growth factor and endothelin-1 stimulated only modest amounts of matrix contraction compared to transforming growth factor beta. CONCLUSIONS Matrix contraction by cells, as observed in the development of tractional forces, can be modulated by a broad-spectrum kinase inhibitor. The marginal contractile responses of choroidal fibroblasts to platelet-derived growth factor and endothelin-1, both potent promoters of dermal fibroblast contraction, suggest that there are substantive difference in the responses of these two cell types to growth factors.