The modulation of transcription factor in liver regeneration after hepatic ischemia/reperfusion

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1. Liver regeneration after hepatic ischemia/reperfusion injury.Activin mRNA expression and serum levels of activin were increased within 1 hour of reperfusion. Follistatin protein levels in serum samples were also increased after reperfusion. These results indicate that activin inhibits initiation of regeneration in hepatocytes at early time point after hepatic ischemia/reperfusion. The activin-follistatin system is one of the important regulatory systems modulating regeneration processes of the liver.2. Hepatic ischemia/reperfusion injury alterations in experimental cholestasis.The mechanism of liver injury in cholestatic liver is not fully understood. Male C57BL/6 mice underwent common bile duct ligation and subsequently developed obstructive cholestasis. The mice were subjected to 90 minutes of partial hepatic ischemia followed by reperfusion. The survival rate of the mice with cholestatic livers after hepatic ischemia/reperfusion was lower than that of the mice with normal livers. … More Biochemical and histological analyses showed that the cholestatic mice had a much higher degree of hepatocellular injury after reperfusion than the normal mice. Neutrophil accumulation after reperfusion was significantly decreased in the cholestatic livers ; however, considerable microcirculatory disturbances were observed in cholestatic livers after reperfusion. Hepatic stellate cell activation and hepatic expression of endothelin-1 were evaluated by immunohistochemical staining in cholestatic livers after reperfusion. These observations were also associated with increased serum levels of endothelin-1. Hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver.3. Clinical examination of liver regeneration.Preoperative portal vein embolization (PVE) is an effective means of creating hypertrophy of future remaining liver, which leads to safety of extensive hepatectomy for hepatic malignancies. Hepatic response to PVE includes the induction of numerous mediators such as growth factors. However, the factors affecting liver regeneration after PVE are not clearly understood. Plasma VEGF levels were increased markedly after PVE and were maximal after 7 days of PVE. Plasma TGF-beta levels were also increased after PVE and peaked at 14 days. % increased liver volume was significantly correlated with plasma VEGF level after 7 days of PVE.. VEGF could affect the activation of regenerative cascade in hepatic remaining lobe after PVE.. Measurement of plasma VEGF levels after PVE may be a predictive factor of potential liver regeneration and may provide useful information to decide on the schedule of subsequent hepatectomy Less