Targeting the Wnt signaling pathway: the challenge of reducing scarring without affecting repair

Introduction: Globally, deaths from liver disease are increasing and for most patients there are few curative options. Fibrosis or scarring is often associated with the formation and progression of liver disease; however, clinical anti-fibrotic therapies are lacking. Recent work has shown that Wnt signaling, a signaling pathway that is necessary for embryonic development and cancer, can also regulate scar formation in the liver.Areas covered: This article seeks to shed light on the dualistic role of Wnt signaling in liver regeneration following injury and how Wnt signaling can regulate scar formation. It also discusses how Wnt signaling cooperates with other classical fibrogenic signaling cascades, such as TGFβ signaling. Finally, the article examines recent advances in the development of Wnt signaling pathway inhibitors and asks whether repurposing these agents as anti-fibrotic therapies is a realistic option.Expert opinion: The understanding of Wnt signaling in liver regeneration and fibrosis is in its infancy and whilst new generations of Wnt pathway inhibitors have shown anti-fibrotic effects, further research is necessary to enhance our understanding of the Wnt-landscape in different patterns of liver disease. This will accelerate the development of more specific Wnt inhibitor-based anti-fibrotics.