Identification of Gene Targets of Activated Sirtuins in Diabetic Wound Healing

Abstract

One of the complications of diabetes is a delay in the healing of wounds, which, if not treated timely, might result in the amputation of lower limbs. Sirtuins have significant functions in regulating a wide range of biological processes, including metabolic diseases and inflammation. Sirtuins 1, 3, and 6 are promising therapeutic targets in treating diabetic wounds. However, the target genes of these situations and their effects on gene expression are yet to be fully understood in diabetic wound healing. This study used lapachol to increase sirtuin levels in diabetic mice. Lapachol is a naphthoquinone and exhibits a broad range of therapeutics. In the in-vivo experiment, a wound was created in diabetic mice, and lapachol was applied topically on the mice skin. Wound contraction was monitored from days 1 to 10. Mice treated with 0.1% lapachol showed the most accelerated wound closure compared to other groups, signifying lapachol healing capability. An in-silico analysis was conducted to find key gene targets of the activated sirtuins involved in diabetic wound healing, and several functional studies were performed using tools and databases such as ShinyGO, Ingenuity Pathway Analysis and Kyoto Encyclopedia of Genes Genomes pathway (KEGG), and Cytoscape analysis. XRCC6, FOXO3, HIF1A, P53, NNT, PPARGC1A, PPARγ, PPARα, and GLUT1 are potential key gene targets of activated sirtuin 1, 3, and 6, which are probably involved in diabetic wound regulation. This can offer therapeutic potential for improving the healing of diabetic wounds.