Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Department of Rheumatology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Cytokine. 2024 Oct;182:156727. doi: 10.1016/j.cyto.2024.156727. Epub 2024 Aug 6.
Growth differentiation factor 15 (GDF15) is a cell stress-response cytokine within the transforming growth factor-β (TGFβ) superfamily. It is known to exert diverse effects on many metabolic pathways through its receptor GFRAL, which is expressed in the hindbrain, and transduces signals through the downstream receptor tyrosine kinase Ret. Since the liver is the core organ of metabolism, summarizing the functions of GDF15 is highly important. In this review, we assessed the relevant literature regarding the main metabolic, inflammatory, fibrogenic, tumorigenic and other effects of GDF15 on different liver diseases, including Metabolic dysfunction-associated steatotic liver disease(MASLD), alcohol and drug-induced liver injury, as well as autoimmune and viral hepatitis, with a particular focus on the pathogenesis of MASLD progression from hepatic steatosis to MASH, liver fibrosis and even hepatocellular carcinoma (HCC). Finally, we discuss the prospects of the clinical application potential of GDF15 along with its research and development progress. With better knowledge of GDF15, increasing in-depth research will lead to a new era in the field of liver diseases.
生长分化因子 15（GDF15）是转化生长因子-β（TGFβ）超家族中的一种细胞应激反应细胞因子。它通过其在后脑表达的受体 GFRAL 对许多代谢途径发挥多种作用，并通过下游受体酪氨酸激酶 Ret 转导信号。由于肝脏是代谢的核心器官，因此总结 GDF15 的功能非常重要。在这篇综述中，我们评估了关于 GDF15 对不同肝病的主要代谢、炎症、纤维化、致瘤和其他作用的相关文献，包括代谢功能障碍相关脂肪性肝病（MASLD）、酒精和药物性肝损伤以及自身免疫性和病毒性肝炎，特别关注了 MASLD 从肝脂肪变性进展为 MASH、肝纤维化甚至肝细胞癌（HCC）的发病机制。最后，我们讨论了 GDF15 的临床应用潜力及其研究和开发进展。随着对 GDF15 的认识不断提高，深入研究将引领肝病领域的新时代。
