RESUMO
The present study was conducted to compare the effects of exogenous follistatin and activin A on liver regeneration in 90% hepatectomized rats. Intraportal administration of follistatin markedly accelerated liver regeneration, and nuclear BrdU labeling and liver regeneration rate were greatly increased by follistatin. In contrast, administration of activin A attenuated liver regeneration. After 120 h of 90% hepatectomy, histological analysis showed that the hepatic architecture was restored in control and activin-treated rats. However, it was not restored in follistatin-treated rats. The serum bilirubin levels were significantly increased in follistatin-treated rats, and the serum glucose level was significantly lower in follistatin-treated rats. Although follistatin markedly accelerated liver regeneration, it reduced the function of the remnant liver. Treatment with activin A instead may be beneficial to support liver regeneration after massive hepatectomy.
Assuntos
Ativinas/uso terapêutico , Folistatina/uso terapêutico , Hepatectomia , Subunidades beta de Inibinas/uso terapêutico , Regeneração Hepática/efeitos dos fármacos , Ativinas/farmacologia , Animais , Bilirrubina/sangue , Glicemia/análise , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Folistatina/farmacologia , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Subunidades beta de Inibinas/farmacologia , Fígado/citologia , Fígado/fisiologia , Fígado/cirurgia , Regeneração Hepática/fisiologia , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND/AIMS: The production of activin A is markedly up-regulated in hepatocytes after partial hepatectomy. This factor tonically inhibits growth of hepatocytes but little is known about its effect on sinusoidal endothelial cells (SEC). In the present study, we investigated whether or not activin A affects growth and differentiation of SEC. METHODS: Growth and survival of SEC were measured in monolayer culture. Capillary formation was studied using SEC cultured in a collagen gel. RESULTS: SEC could not survive in the absence of vascular endothelial growth factor (VEGF). Activin A had a small effect on prevention of cell death and also enhanced anti-apoptotic action of VEGF. In addition, activin A and VEGF acted synergistically to stimulate cell growth of SEC. In the collagen gel, VEGF induced capillary formation of SEC. Activin A had little effect on branching tubulogenesis by itself but markedly enhanced tubular formation induced by VEGF. Finally, VEGF induced the expression of activin A and activin A increased the expression of VEGF receptors in cultured SEC. CONCLUSIONS: Activin A augments VEGF activity in promoting growth and tubulogenesis of SEC.