GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential

Liver fibrosis is a chronic pathological process driven by the activation of hepatic stellate cell (HSC) and characterized by the excessive deposition of extracellular matrix (ECM) components in response to persistent liver injury. This condition can lead to progressive hepatic dysfunction, cirrhosis, and ultimately liver failure. Growth differentiation factor 15 (GDF15) has emerged as a pivotal regulator in the initiation and progression of liver fibrosis, exhibiting context-dependent profibrotic and antifibrotic effects. GDF15 modulates multiple cellular processes, including HSC activation and macrophage polarization, as well as the functions of T cells, natural killer cells, B cells and mesenchymal stem cells. This review provides a comprehensive overview of the role of GDF15 in regulating HSC activation and immune cell responses and elaborates on its immunomodulatory functions in attenuating liver fibrosis. Furthermore, we discuss the therapeutic potential of targeting GDF15 for the treatment of liver fibrosis. Ultimately, this review aims to provide a theoretical foundation and propose novel intervention strategies for the early diagnosis and targeted therapy of liver fibrosis.