Epidermal growth factor stimulates proton efflux from chondrocytic cells
Epidermal growth factor stimulates proton efflux from chondrocytic cells
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DOI：
10.1002/jcp.10120
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发表时间：
2002-07-01
影响因子：
5.6
通讯作者：
Bernier, SM
中科院分区：
文献类型：
--
作者：
Lui, KEH;Panchal, AS;Bernier, SM
来自软骨细胞的质子外排改变了软骨的细胞外pH值和离子组成，并影响细胞外基质的合成和降解。表皮生长因子（EGF）在骨骼发育过程中促进软骨细胞增殖，并在类风湿性关节炎的滑液中积累。本研究的目的是探讨EGF对软骨细胞质子外排的影响。当使用细胞传感器微生理仪监测时，发现EGF可快速激活CFK2软骨细胞和大鼠关节软骨细胞的质子外排。EGF的作用呈浓度依赖性，在0.3 ~ 0.7 ng/ml时达到半效。反复暴露于EGF后，观察到部分脱敏和随时间变化的反应恢复。egf诱导的质子外排依赖于细胞外葡萄糖，Na+/H+交换（NHE）抑制剂显著减弱了质子外排的初始增加。磷脂酰肌醇3-激酶和磷脂酶C的抑制剂会减弱反应，但MEK （MAPK/ERK激酶）或蛋白激酶A或C的抑制剂不会减弱反应。因此，egf诱导的质子外排涉及葡萄糖代谢和NHE，并由egf激活的信号通路的一个离散亚群调节。在体内，ECF诱导的质子外排可能导致酸性环境，促进软骨基质在发育过程中的周转和类风湿关节炎。(C) 2002 Wiley-Liss, Inc。
Proton efflux from chondrocytes alters the extracellular pH and ionic composition of cartilage, and influences the synthesis and degradation of extracellular matrix. Epidermal growth factor (EGF) promotes chondrocyte proliferation during skeletal development and accumulates in the synovial fluid in rheumatoid arthritis. The purpose of this study was to investigate the effect of EGF on proton efflux from chondrocytes. When monitored using a Cytosensor microphysiometer, EGF was found to rapidly activate proton efflux from CFK2 chondrocytic cells and rat articular chondrocytes. The actions of EGF were concentration-dependent with half-maximal effects at 0.3-0.7 ng/ml. Partial desensitization and time-dependent recovery of the response were observed following repeated exposures to EGF. EGF-induced proton efflux was dependent on extracellular glucose, and inhibitors of Na+/H+ exchange (NHE) markedly attenuated the initial increase in proton efflux. The response was diminished by inhibitors of phosphatidylinositol 3-kinase and phospholipase C, but not by inhibitors of MEK (MAPK/ERK kinase) or protein kinase A or C. Thus, EGF-induced proton efflux involves glucose metabolism and NHE, and is regulated by a discrete subset of EGF-activated signaling pathways. In vivo, proton efflux induced by ECF may lead to an acidic environment, enhancing turnover of cartilage matrix during development and in rheumatoid arthritis. (C) 2002 Wiley-Liss, Inc.