Hedgehog signaling pathway as key player in liver fibrosis: new insights and perspectives

Introduction: Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in liver fibrosis. Therefore, improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for liver fibrosis. Greater knowledge of the role of the hedgehog signaling pathway in liver fibrosis could improve understanding of the liver fibrosis pathogenesis. Areas covered: The aim of this review is to describe the present knowledge about the hedgehog signaling pathway, which significantly participates in liver fibrosis and HSC activation, and look ahead on new perspectives of hedgehog signaling pathway research. Moreover, we will discuss the different interactions with hedgehog signaling pathway-regulated liver fibrosis. Expert opinion: The hedgehog pathway modulates several important aspects of function, including cell proliferation, activation and differentiation. Targeting the hedgehog pathway can be a promising direction in liver fibrosis treatment. We discuss new perspectives of hedgehog signaling pathway activation in liver fibrosis and HSC fate, including DNA methylation, methyl CpG binding protein 2, microRNA, irradiation and metabolism that influence hedgehog signaling pathway transduction. These findings identify the hedgehog pathway as a potentially important for biomarker development and therapeutic targets in liver fibrosis. Future studies are needed in order to find safer and more effective hedgehog-based drugs.