Brg1 promotes liver regeneration after partial hepatectomy via regulation of cell cycle

Abstract

Brahma-related gene 1 (Brg1), a catalytic subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, is known to be involved in proliferative cell processes. Liver regeneration is initiated spontaneously after injury and leads to a strong proliferative response. In this study, a hepatocyte-specific Brg1 gene knockout mouse model was used to analyse the role of Brg1 in liver regeneration by performing a 70% partial hepatectomy (PH). After PH, Brg1 was significantly upregulated in wildtype mice. Mice with hepatocyte-specific Brg1 gene knockout showed a significantly lower liver to body weight ratio 48 h post-PH concomitant with a lower hepatocellular proliferation rate compared to wildtype mice. RNA sequencing demonstrated that Brg1 controlled hepatocyte proliferation through the regulation of the p53 pathway and several cell cycle genes. The data of this study reveal a crucial role of Brg1 for liver regeneration by promoting hepatocellular proliferation through modulation of cell cycle genes and, thus, identify Brg1 as potential target for therapeutic approaches.