Nature：武汉大学宋保亮院士团队发现MASH防治新靶点，并提出治疗方法

Core Viewpoint - The research identifies the GPNMB-RYK signaling axis as a novel pathogenic ligand-receptor pathway and a promising therapeutic target for Metabolic Dysfunction-Associated Steatotic Hepatitis (MASH) [5] Group 1: Research Findings - MASH is a critical stage of Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) with increasing global prevalence and limited treatment options [3] - The study published in Nature reveals that the extracellular domain of GPNMB (G-ECD) drives the progression of MASH by promoting fat accumulation and inflammation in the liver [3][4] - The research team found that knocking out the Gpnmb gene in mice protects them from diet-induced MASH, indicating the gene's significant upregulation in MASH [4] Group 2: Mechanism of Action - The binding of G-ECD to the RYK receptor activates the ERK1/2 signaling pathway, leading to the transcriptional activation of PPARγ-CD36 and SREBP1C pathways, which promote lipid uptake and synthesis in the liver [4] - The study confirmed that various therapeutic strategies targeting the GPNMB-RYK signaling axis, including G-ECD vaccines and AAV-delivered shRNA, effectively prevent and treat MASH in preclinical models [4]