Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
J Drug Target. 2022 Nov;30(9):911-926. doi: 10.1080/1061186X.2022.2085729. Epub 2022 Jul 12.
Sirtuins are a vast family of histone deacetylases, which are NAD dependent enzymes, consisting of seven members, namely SIRT 1, SIRT 6 and SIRT 7 located within the nucleus, SIRT 2 in the cytoplasm and SIRT 3, SIRT 4 and SIRT 5 in the mitochondria. They have vital roles in regulating various biological functions such as age-related metabolic disorders, inflammation, stress response, cardiovascular and neuronal functions. Delayed wound healing is one of the complication of diabetes, which can lead to lower limb amputation if not treated timely. SIRT 1, 3 and 6 are potent targets for diabetic wound healing. SIRT 1 deficiency reduces recruitment of fibroblasts, macrophages, mast cells, neutrophils to wound site and delays wound healing; negatively expressing MMP-9. The SIRT 1 mediated signalling pathway in diabetic wound healing is the SIRT 1-FOXO-c-Myc pathway. On the contrary, SIRT 3 deficiency impairs proliferation and migration of fibroblasts and SIRT 6 deficiency impairs wound closure rate and interrupts the vascular remodelling. This review focuses on the role of sirtuins in improving delayed wound healing in diabetes and its natural modulators with their specific functions towards healing diabetic wounds.
去乙酰化酶是一个庞大的组蛋白家族，是 NAD 依赖性酶，由 7 个成员组成，分别是位于核内的 SIRT1、SIRT6 和 SIRT7、位于细胞质中的 SIRT2 以及位于线粒体中的 SIRT3、SIRT4 和 SIRT5。它们在调节各种生物功能方面发挥着重要作用，如与年龄相关的代谢紊乱、炎症、应激反应、心血管和神经元功能。伤口愈合延迟是糖尿病的并发症之一，如果不及时治疗，可能导致下肢截肢。SIRT1、SIRT3 和 SIRT6 是糖尿病伤口愈合的有效靶点。SIRT1 缺乏会减少成纤维细胞、巨噬细胞、肥大细胞、中性粒细胞向伤口部位的募集，并延迟伤口愈合；负向表达 MMP-9。糖尿病伤口愈合中的 SIRT1 介导的信号通路是 SIRT1-FOXO-c-Myc 通路。相反，SIRT3 缺乏会损害成纤维细胞的增殖和迁移，而 SIRT6 缺乏会损害伤口闭合率并中断血管重塑。本综述重点介绍了 Sirtuins 在改善糖尿病中伤口愈合延迟的作用及其天然调节剂及其对愈合糖尿病伤口的特定功能。
