How the liver regenerates after injury

The mammalian liver possesses the remarkable ability to regenerate after injury, potentially restoring up to 70% of its lost mass and function in just a few weeks. But the underlying mechanisms that drive the proliferation of liver cells after injury remain poorly defined. A recent study revealed an important role for the epithelial splicing regulatory protein 2 (ESRP2) and the Hippo signaling pathway in liver regeneration. Deletion of ESRP2 in mouse livers results in excessive proliferation of liver cells upon injury. Specifically, downregulation of ESRP2 rewires the Hippo signaling pathway in regenerating liver cells. By contrast, maintaining high ESRP2 expression during toxin exposure blocks proliferation. In the future, it may be possible to therapeutically harness the novel ESRP2-Hippo pathway to stimulate regeneration during acute liver failure or end-stage liver disease. The study, which was partly funded by the NHLBI, was published in the journal Nature Structural & Molecular Biology.