Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, 60637, USA.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Sci Rep. 2017 Oct 26;7(1):14110. doi: 10.1038/s41598-017-14371-3.
Sirtuins (SIRT1-7) are NAD-dependent proteins with the enzymatic activity of deacetylases and ADP ribosyltransferases. SIRT1 is the proto member of the proteins in the mammalian sirtuin family and plays multiple roles in aging and disease. Using mice with epidermis-specific SIRT1 deletion, we show that SIRT1 is required for efficient wound healing. SIRT1 deficiency in the epidermis inhibited the regeneration of both the epidermis and the dermal stroma. SIRT1 loss altered the production of many cytokines, inhibited the recruitment of macrophages, neutrophils, and mast cells, the recruitment and activation of fibroblasts, and angiogenesis in the granulation tissue. In keratinocytes, SIRT1 knockdown inhibited EMT, cell migration, and TGF-β signaling. For the first time, using skin-specific mouse model, we demonstrate that epidermal SIRT1 plays a crucial role in wound repair. These findings are novel in understanding how wound healing is regulated. Our findings provide in vivo and in vitro evidence that SIRT1 in the epidermis regulates cell migration, redox response, inflammation, epidermis re-epithelialization, granulation formation, and proper wound healing in mice.
沉默调节蛋白（SIRT1-7）是一种 NAD 依赖性蛋白，具有去乙酰化酶和 ADP 核糖基转移酶的酶活性。SIRT1 是哺乳动物沉默调节蛋白家族中蛋白的原成员，在衰老和疾病中发挥多种作用。使用表皮特异性 SIRT1 缺失的小鼠，我们表明 SIRT1 是伤口愈合所必需的。表皮中的 SIRT1 缺乏抑制了表皮和真皮基质的再生。SIRT1 丧失改变了许多细胞因子的产生，抑制了巨噬细胞、中性粒细胞和肥大细胞的募集，成纤维细胞的募集和激活，以及肉芽组织中的血管生成。在角质形成细胞中，SIRT1 的敲低抑制了 EMT、细胞迁移和 TGF-β 信号转导。首次使用皮肤特异性小鼠模型，我们证明了表皮 SIRT1 在伤口修复中起着至关重要的作用。这些发现对于理解伤口愈合是如何被调节的具有新颖性。我们的研究结果提供了体内和体外证据，表明表皮中的 SIRT1 调节细胞迁移、氧化还原反应、炎症、表皮再上皮化、肉芽形成和小鼠的适当伤口愈合。
