EXPRESSION OF THE NA+ CA2+ EXCHANGER EMERGES IN HEPATIC STELLATE CELLS AFTER ACTIVATION IN ASSOCIATION WITH LIVER FIBROSIS/

Activation of hepatic stellate (Ito) cells is a final common pathway o f liver fibrosis, The findings presented in this paper indicate that e xpression of Na+/Ca2+ exchanger (NCX) emerges in rat hepatic stellate cells after activation in vitro during primary culture or in vivo in r esponse to intoxication with CCl4. NCX mRNA became detectable by North ern blot analysis in cultured stellate cells on day 3, as was alpha-sm ooth muscle actin, an indicator not only of smooth muscle differentiat ion but also of stellate cell activation. Western blot analysis showed expression of the exchanger protein in the activated stellate cells. Functional expression of the exchanger, monitored by Ni2+-sensitive, v erapamil-insensitive intracellular free Ca2+ increases in response to reduction of extracellular Na+ concentration, became sizable by using Fura-2 in stellate cells by 7 days in culture, Furthermore, increased expression of the exchanger mRNA was found predominantly in stellate c ells freshly isolated from the CCl4 model rat of hepatic fibrosis, Thu s, it is concluded that NCX expression is closely associated with acti vation of hepatic stellate cells in vitro and in vivo. Because, even a t the whole liver level, increased expression of NCX mRNA became obser vable after induction of liver fibrosis, it is suggested that NCX expr ession serves a useful diagnostic marker of liver fibrosis or cirrhosi s.