四川大学最新Cell：揭开肝纤维化新机制并研发出首创新药，已开展人体临床试验

Core Viewpoint - The research highlights the pathogenic role of upregulated ROCK2 in liver fibrosis and emphasizes the importance of the vascular microenvironment in the progression of fibrosis, leading to the development of a selective ROCK2 inhibitor, TDI01, which shows promise in treating liver fibrosis [4][6][9]. Group 1 - The study reveals that the upregulation of ROCK2 in hepatic stellate cells and endothelial cells contributes to vascular microenvironment dysfunction and promotes fibrosis through angiocrine signaling [4][6]. - The research team developed TDI01, a highly selective ROCK2 inhibitor, which demonstrated good safety and antifibrotic potential in preclinical models and human liver fibrosis patients [4][6]. - TDI01 showed a trend of fibrosis reduction in 5 out of 6 liver fibrosis patients, with improvements in liver stiffness, collagen deposition, and fibrosis staging [6][9]. Group 2 - The study establishes ROCK2 as a druggable target for antifibrotic therapy in metabolic-associated steatotic liver disease (MASH) [9]. - The selective ROCK2 inhibitor TDI01 effectively blocked liver fibrosis in rodent and miniature pig models of MASH [9]. - The first-in-class drug development process from target discovery to clinical research is outlined, providing a theoretical and practical basis for targeting angiocrine functions in antifibrotic treatment [4][6].