Hedgehog signaling in the liver

The Hedgehog signaling pathway regulates tissue patterning during development. Because it is barely active in healthy adult livers, the Hedgehog pathway was generally presumed to be irrelevant in adult livers. However, that dogma was shattered by the demonstration that Hedgehog signaling is routinely reactivated after liver injury, and evidence that it controls various wound-healing responses. In fact, the Hedgehog pathway plays a critical role orchestrating liver repair, promoting progenitor cell proliferation to replace lost epithelial cells and activating stellate cells, immune cells, and endothelial cells to optimize the local microenvironment for repair. With improved understanding of Hedgehog's roles in injured adult livers has come the realization that modulating Hedgehog signaling provides a promising therapeutic approach for liver disease. In this chapter we will review the literature on the Hedgehog pathway in the liver, with particular focus on its role in regeneration, chronic liver disease, and cancer.

Duke Scholars

Author Anna Mae Diehl Medicine, Gastroenterology