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

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.