title: 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.
abstract: OBJECTIVE
  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, insulin-like growth factor 1 (IGF-1) and insulin.
  
  
  RESULTS
  pH(i) regulation was mainly dependent on the activity of the Na+/H+ exchanger, which was evaluated by measuring pH(i) 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-1 (10 nmol/l), but not insulin (100 nmol/l), slightly but significantly increased the activity of the Na+/H+ exchanger. Amiloride (100 micromol/l) and 20 micromol/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-1, whereas the proliferative effect of insulin is mediated by intracellular pathways which are Na+/H+ exchange-independent.
authors.affiliation: Department of Gastroenterology, University of Ancona, Nuovo Polo Didattico, Torrette, Italy. clingastro@popcsi.unian.it
authors.forename: A
authors.initials: A
authors.lastname: Di Sario
authors.forename: G
authors.initials: G
authors.lastname: Svegliati Baroni
authors.forename: E
authors.initials: E
authors.lastname: Bendia
authors.forename: F
authors.initials: F
authors.lastname: Ridolfi
authors.forename: S
authors.initials: S
authors.lastname: Saccomanno
authors.forename: L
authors.initials: L
authors.lastname: Ugili
authors.forename: L
authors.initials: L
authors.lastname: Trozzi
authors.forename: M
authors.initials: M
authors.lastname: Marzioni
authors.forename: A M
authors.initials: AM
authors.lastname: Jezequel
authors.forename: G
authors.initials: G
authors.lastname: Macarri
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
mesh_terms: D001639:Bicarbonates / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D017923:Sodium-Hydrogen Exchangers; D007334:Insulin-Like Growth Factor I; D006859:Hydrogen