LAUSR

The past 30 years have seen major progress in the knowledge plays a fundamental role in fibrogenesis,mainly by inducingHSC activaand management of liver disease. Unfortunately, millions of people worldwide still suffer from chronic hepatic illness. The incidence and prevalence of fibrosis, leading to cirrhosis, which may predispose people to liver cancer, is key to understanding the burden of liver disease. Liver fibrosis can be induced by nonalcoholic liver disease (40%), hepatitis B virus (30%), hepatitis C virus (15%), and harmful alcohol consumption (11%) [1]. Fibrosis and cirrhosis represent the end stage of liver pathology and thus are indicative of the associated mortality. The projection of cirrhosis and liver cancer until 2030 clearly shows that these hepatic pathologies are increasing as an international cause of death [1]. However, no antifibrotic therapy has been approved to date. The activation or transdifferentiation of hepatic stellate cells (HSCs), which are the major drivers of liver fibrogenesis, is the most important step triggering the deposition of exacerbated amounts of extracellular matrix (ECM) proteins. Cell type and target-specific pharmacological intervention to therapeutically induce the deactivation of HSCs will enable more effective and less toxic precision antifibrotic therapies [2]. In this regard, the role of collagen triple helix repeat containing 1 (CTHRC1) protein, which is involved in many physiological and pathological processes [3,4], in the activation of HSCs was investigated by Li et al. [5]. Interestingly, they found, for the first time, that CTHRC1 is an important regulator of hepatic fibrogenesis. CTHRC1 protein is secreted by HSCs and was found to be significantly upregulated in fibrotic liver tissues derived from chronically thioacetamide or CCl4-treated rodents. Moreover, CTHRC1 induced the transdifferentiation of HSCs to the active ECM secreting type and increased the contractile and migratory ability of the activated HSCs through the TGF-β pathway. The authors also found that CTHRC1 bound to a noncanonical Wnt receptor in a competitivemanner, thus promoting the contractility of HSCs. They corroborated their results by administering CCl4 or TAA to CTHRC−/− mice and found thatfibrosiswas less evident in thesemice than in littermate controls; moreover, a monoclonal antibody against CTHRC1 suppressed hepatic ECM deposition in WT mice treated with these chemical inductors of fibrosis. In summary, Li, et al. found, for the first time, that CTHRC1 is a new regulator of liver fibrosis that acts bymodulating TGF-β signaling [5]. TGF-β is a potent pro-fibrogenic factor that