Intracellular pH regulation and Na+/H+ exchange activity in human hepatic stellate cells:: effect of platelet-derived growth factor, insulin-like growth factor 1 and insulin
Intracellular pH regulation and Na+/H+ exchange activity in human hepatic stellate cells:: effect of platelet-derived growth factor, insulin-like growth factor 1 and insulin
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DOI：
10.1016/s0168-8278(00)00062-3
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发表时间：
2001-03-01
影响因子：
25.7
通讯作者：
Benedetti, A
中科院分区：
文献类型：
--
作者：
Di Sario, A;Baroni, GS;Benedetti, A
背景/目标：Na~+/H~+交换参与了血小板衍生生长因子（PDGF）诱导的大鼠肝星状细胞（HSC）增殖，因此我们在人HSC中评价了：（1）细胞内pH调节机制;（2）Na~+/H~+交换激活与PDGF、胰岛素样生长因子1（IGF-1）和胰岛素诱导的细胞增殖的关系。pH（i）调节主要依赖于Na +/H+交换器的活性，其通过测量从急性酸负荷的pHi恢复来评估。PDGF（25 ng/ml）逐渐增加Na~+/H~+交换体的活性，18 h达高峰，24 h保持稳定; IGF-1（10 nmol/l）轻微但显著增加Na~+/H~+交换体的活性，而胰岛素（100 nmol/l）无此作用。amiloride（100 μ mol/l）和20 μ mol/l 5-N-乙基-N-异丙基-阿米洛利完全抑制HSC增殖（通过测量溴脱氧尿苷掺入来评估），但不影响胰岛素诱导的HSC增殖，最后，IGF-1不改变Na +/Ca 2+交换器的活性。Na +/H+交换参与PDGF和IGF-I诱导的HSC增殖，而胰岛素的增殖作用是通过不依赖于Na +/H+交换的细胞内途径介导的。(C)2001年欧洲肝脏研究协会。由Elsevier Science B，V出版，保留所有权利。
Background/Aims: The Na+/H+ exchanger is involved in rat hepatic stellate cell (HSC) proliferation induced by platelet-derived growth factor (PDGF), We therefore evaluated in human HSC: (1) the mechanisms of intracellular pH regulation; (2) the relationship between Na+/H+ exchange activation and cell proliferation induced by PDGF, insulinlike growth factor 1 (IGF-1) and insulin.Methods/Results: pH(i) regulation was mainly dependent on the activity of the Na+/H+ exchanger, which was evaluated by measuring pHi recovery from an acute acid load. PDGF (25 ng/ml) gradually increased the activity of the Na+/H+ exchanger which peaked at 18 h and remained stable until the 24th h, IGF-I (10 nmol/l), but not insulin (100 nmol/l), slightly but significantly increased the activity of the Na+/H+ exchanger. Amiloride (100 mu mol/l) and 20 mu mol/l 5-N-ethyl-N-isopropyl-amiloride completely inhibited HSC proliferation (evaluated by measurement of bromodeoxyuridine incorporation) induced by PDGF and IGF-1, but did not affect proliferation of HSC induced by insulin, Finally, IGF-1 did not modify the activity of the Na+/Ca2+ exchanger.Conclusions: The Na+/H+ exchanger is involved in HSC proliferation induced by PDGF and IGF-I, whereas the proliferative effect of insulin is mediated by intracellular pathways which are Na+/H+ exchange-independent.(C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B,V, All rights reserved.