Circulating indian hedgehog is a marker of the hepatocyte-TAZ pathway in experimental NASH and is elevated in humans with NASH

• DOI: 10.1016/j.jhepr.2023.100716
• Publication Date: 2023-02-26T21:16:45Z
• Authors: Mary Patricia Moore; Xiaobo Wang; Hongxue Shi; Marica Meroni; Alessandro Cherubini; Luisa Ronzoni; Elizabeth J. Parks; Jamal A. Ibdah; R. Scott Rector; Luca Valenti; Paola Dongiovanni; Ira Tabas
• Keywords: Steatohepatitis; Indian hedgehog; Liver disease

Background & Aims: Non-alcoholic steatohepatitis (NASH)-induced liver fibrosis is emerging as the most common cause of disease.For evaluation therapies, there a pressing need to identify non-invasive, mechanism-based biomarkers.A pro-fibrotic process relevant human NASH involves pathway in which transcriptional regulator called TAZ (WWTR1) hepatocytes induces secretion Indian hedgehog (IHH).We therefore reasoned that circulating IHH may be useful marker assess changes fibrosis.Methods: Circulating was assessed wild-type and hepatocyte-TAZ-silenced mice three separate cohorts patients with mild-moderate NASH.Results: elevated diet-induced compared chow-fed or hepatocyte silenced, an effective means decrease fibrosis.In fatty disease without NASH, associated increased concentrations IHH.Conclusions: The results these analyses support further investigation determine whether indicator target engagement anticipated future clinical trials testing therapies block pathway.Impact implications: disease.Circulating biomarkers reflect would very evaluate therapies.One mechanism potential therapeutic liver-secreted protein report levels experimental associates NASH-associated fibrosis, providing premise for into using liver.