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.
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.
Di Sario
A
A
Department of Gastroenterology, University of Ancona, Nuovo Polo Didattico, Torrette, Italy. clingastro@popcsi.unian.it
Svegliati Baroni
G
G
Bendia
E
E
Ridolfi
F
F
Saccomanno
S
S
Ugili
L
L
Trozzi
L
L
Marzioni
M
M
Jezequel
A M
AM
Macarri
G
G
Benedetti
A
A
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*
D001639:Bicarbonates; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D017923:Sodium-Hydrogen Exchangers; D007334:Insulin-Like Growth Factor I; D006859:Hydrogen