The study of liver regeneration in ahnak knock-out mice

Abstract

Ahnak is a 700kDa giant protein that is initially identified in human neuroblastoma and other cancer cells. The carboxyl-terminal of ahnak domain implicates diverse functions such as signal transduction and calcium homeostasis. Even though, there have been several papers for elucidating the biological role of ahnak involved in cell cycle and cancer cells. However still, there is no report on the role of ahnak during liver regeneration. Also, it is well known that intracellular calcium is essential for the transition from resting to proliferative state during liver regeneration. In rodent model, the rapid restoration of the liver mass provides a model for studying cell cycle. Therefore, the liver regeneration was examined in ahnak knock-out mice after 70% partial hepatectomy. The number of PCNA (proliferating cell nuclear antigen) positive cells was higher in ahnak knock-out mice than wild type mice at 24, 48 and 72hrs after hepatectomy. It was significantly increased in ahnak knock-out mice at 48 hrs after hepatectomy. Comparing with ahnak wild type mice, liver mass restoration in ahnak knock-out mice was accelerated, which was associated with increased expression levels in immediate early gene c-myc, c-fos, c-jun. Accordingly, cell cycle related proteins, including cyclin D1, PCNA, and CDK4 (cyclin dependent kinase 4) were increased in the liver of ahnak knock-out mice compared wild type mice at 24, 48 and 72hrs after hepatectomy. Our results indicate that ahnak is an important role in the liver regeneration in vivo. Cell cycle signaling pathways associated with ahnak may provide new insights for improved understanding of liver regeneration. The exact mechanism of accelerated liver regeneration driven by functional loss of ahnak should be elucidated.