School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China.
Cancer Hospital of The University of Chinese Academy of Sciences, Hangzhou, China.
Pharmacol Ther. 2022 Jan;229:107983. doi: 10.1016/j.pharmthera.2021.107983. Epub 2021 Sep 2.
Fibrosis, which is characterized by excessive extracellular matrix (ECM) deposition, is a wound-healing response to organ injury and may promote cancer and failure in various organs, such as the heart, liver, lung, and kidney. Aging associated with oxidative stress and inflammation exacerbates cellular dysfunction, tissue failure, and body function disorders, all of which are closely related to fibrosis. Sirtuin-1 (SIRT1) is a class III histone deacetylase that regulates growth, transcription, aging, and metabolism in various organs. This protein is downregulated in organ injury and fibrosis associated with aging. Its expression and distribution change with age in different organs and play critical roles in tissue oxidative stress and inflammation. This review first described the background on fibrosis and regulatory functions of SIRT1. Second, we summarized the relationships of SIRT1 with other proteins and its protective action during fibrosis in the heart, liver, lung and kidney. Third, the activation of SIRT1 in therapies of tissue fibrosis, especially in liver fibrosis and aging-related tissue injury, was analyzed. In conclusion, SIRT1 targeting may be a new therapeutic strategy in fibrosis.
纤维化的特征是细胞外基质（ECM）的过度沉积，是一种对器官损伤的愈合反应，可能会促进癌症的发生，并导致心脏、肝脏、肺和肾脏等各种器官的衰竭。与氧化应激和炎症相关的衰老会加剧细胞功能障碍、组织衰竭和身体功能障碍，所有这些都与纤维化密切相关。Sirtuin-1（SIRT1）是一种 III 类组蛋白去乙酰化酶，可调节各种器官的生长、转录、衰老和代谢。这种蛋白质在与衰老相关的器官损伤和纤维化中表达下调。它在不同器官中的表达和分布随年龄而变化，在组织氧化应激和炎症中发挥关键作用。这篇综述首先描述了纤维化的背景以及 SIRT1 的调节功能。其次，我们总结了 SIRT1 与其他蛋白质的关系及其在心脏、肝脏、肺和肾脏纤维化中的保护作用。第三，分析了 SIRT1 在组织纤维化治疗中的作用，特别是在肝纤维化和与衰老相关的组织损伤治疗中的作用。总之，靶向 SIRT1 可能是纤维化的一种新的治疗策略。
