Survivin deficient liver of mice after partial hepatectomy. Mus musculus

The liver possesses remarkable regenerative capacity in response to injury. Upon partial hepatectomy (PHx), terminally differentiated hepatocytes in the remaining liver enter the cell cycle and restore the liver mass and function within weeks. However, liver regeneration is often impaired in livers with chronic diseases. Survivin, an inhibitor of apoptosis protein (IAP) and member of chromosome passenger complex (CPC), plays versatile roles in cell mitosis and apoptosis. We and others found that the expression of Survivin was highly increased in liver during PHx-induced liver regeneration, which indicated that Survivin played important roles in this process. However, the function of Survivin in liver regeneration remains largely undefined. Here, using mice with genetic deletion of Survivin, we found that during PHx-induced liver regeneration Survivin regulated both hepatocyte G1/S phase transition by inhibiting the expression of p21 and G2/M phase transition by regulating the localization of CPC. Moreover, restoration of Survivin expression in Survivin-deficient hepatocytes inhibited p21 expression and promote both hepatocyte G1/S and G2/M transition during PHx-induced liver regeneration. Overall design: Four samples are Survivin deleted liver, 0, 24, 36, 48 hours after PHx separately; four samples are Survivin wild type liver, 0, 24, 36, 48 hours after PHx separately.