Brahma compensates the role of brahma-related gene 1 in liver regeneration of albumin-Cre; brahma-related gene 1loxP/loxP mice

摘要

Background: Brahma-related gene 1 and brahma, which are catalytic components of the mammalian chromatin remodeling complex, express ubiquitously in mammalian tissues, including the liver. Although both are involved in numerous biological processes, including cell growth, proliferation, and tumorigenesis, their roles in liver regeneration are still unclear. Methods: We developed special knockout mice in which brahma-related gene 1 was deleted in the hepatocytes. After that, partial hepatectomy and chemical injury models were used to investigate the regulation process in liver regeneration. Results: Notably, brahma-related gene 1 increased in liver regeneration following hepatic injury; however, the loss of brahma-related gene 1 neither prominently disturbed the development, growth, and metabolism of the liver nor impaired liver regeneration even after inducing tumorigenesis. In contrast, the brahma expression maintained at stable levels in the early phase of liver regeneration. Intriguingly, additional brahma silencing in mice through short-hairpin ribonucleic acid decreased the proliferation of hepatocytes, resulting in delayed liver regeneration. Conclusions: In contrast to the accepted notion that brahma could compensate the role of brahma-related gene 1 in liver regeneration by increasing its expression volume, the results of this study found that the deficiency of both brahma-related gene 1 and brahma significantly delays liver regeneration.