Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China; Shanghai Zhangjiang Institute of Medical Innovation, Shanghai 201204, China.
Pharmacol Res. 2023 Jan;187:106604. doi: 10.1016/j.phrs.2022.106604. Epub 2022 Dec 9.
Fibrosis is a common pathological feature of organ diseases resulting from excessive production of extracellular matrix, which accounts for significant morbidity and mortality. However, there is currently no effective treatment targeting fibrogenesis. Recently, metabolic alterations are increasingly considered as essential factors underlying fibrogenesis, and especially research on metabolic regulation of amino acids is flourishing. Among them, branched-chain amino acids (BCAAs) are the most abundant essential amino acids, including leucine, isoleucine and valine, which play significant roles in the substance and energy metabolism and their regulation. Dysregulation of BCAAs metabolism has been proven to contribute to numerous diseases. In this review, we summarize the metabolic regulation of fibrosis and the changes in BCAAs metabolism secondary to fibrosis. We also review the effects and mechanisms of the BCAAs intervention, and its therapeutic targeting in hepatic, renal and cardiac fibrosis, with a focus on the fibrosis in liver and associated hepatocellular carcinoma.
纤维化是器官疾病的一种常见病理特征，其是由细胞外基质过度产生引起的，这导致了相当高的发病率和死亡率。然而，目前针对纤维化发生还没有有效的治疗方法。最近，代谢改变被越来越多地认为是纤维化发生的重要因素，特别是氨基酸代谢调控的研究方兴未艾。其中，支链氨基酸（BCAAs）是最丰富的必需氨基酸，包括亮氨酸、异亮氨酸和缬氨酸，它们在物质和能量代谢及其调节中发挥重要作用。现已证明，BCAAs 代谢失调与许多疾病有关。在这篇综述中，我们总结了纤维化的代谢调控以及纤维化引起的 BCAAs 代谢变化。我们还回顾了 BCAAs 干预的效果和机制，以及其在肝、肾和心脏纤维化中的治疗靶向作用，重点关注肝脏纤维化及其相关的肝癌。
