Department of Burn, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Oxid Med Cell Longev. 2022 Apr 27;2022:1619651. doi: 10.1155/2022/1619651. eCollection 2022.
Sirtuin 6 (SIRT6) is an NAD-dependent deacetylase belonging to the sirtuin family. It has been shown to participate in wound healing and some inflammation-related disorders. However, the effect of MDL-800, a highly efficient and selective SIRT6 activator, on wound healing and inflammation has not been reported. Therefore, this study investigated whether MDL-800 confers anti-inflammatory effects and promotes wound healing and uncovered the molecular mechanisms involved. This was achieved using mouse models of full-thickness wounds. Results showed that MDL-800 significantly downregulated inflammation by attenuating the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds, thereby accelerating cutaneous wound healing. Furthermore, MDL-800 significantly downregulated expression levels of TNF- and IL-6 in the dorsal skin tissue of mice via the NF-B pathway. These results demonstrated that MDL-800 exerted anti-inflammatory and prohealing effects, indicating that the SIRT6/NF-B/IB signaling pathway may play an important role in wound healing.
Sirtuin 6 (SIRT6) 是一种 NAD 依赖性去乙酰化酶，属于 sirtuin 家族。已有研究表明，SIRT6 参与了伤口愈合和一些与炎症相关的疾病。然而，高效且选择性的 SIRT6 激活剂 MDL-800 对伤口愈合和炎症的影响尚未见报道。因此，本研究探讨了 MDL-800 是否具有抗炎作用，以及是否能促进伤口愈合，并揭示了相关的分子机制。这是通过使用全层皮肤伤口的小鼠模型来实现的。结果表明，MDL-800 通过抑制炎症介质的释放显著下调炎症反应，改善胶原沉积和伤口新生血管化，从而加速皮肤伤口愈合。此外，MDL-800 通过 NF-B 通路显著下调了小鼠背部皮肤组织中 TNF-和 IL-6 的表达水平。这些结果表明，MDL-800 具有抗炎和促愈合作用，表明 SIRT6/NF-B/IB 信号通路可能在伤口愈合中发挥重要作用。
