Abstract 269: Sirt-6 Deficiency Impairs Wound Healing in Diabetic (db/db) Mice Through Enhancement of Nf-kb Dependent Transcriptional Activity
Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous physiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However the role of sirtuin 6 (SIRT6), a NAD+-dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyze the role of SIRT6 in cutaneous wound healing, paired 6 mm stented wound were created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and non-sensed siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and western blotting. SIRT6-siRNA treated diabetic wound showed impaired healing, which was associated with reduced capillary density when compared to control treatment. Interestingly, SIRT6 deficiency decreased VEGF expression in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes NF-kB activation resulting in increased expression of proinflammatory marker and oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wounds promotes proinflammatory response by increasing NF-kB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that activation of SIRT6 signaling might be a potential approach for promoting wound healing in diabetics.
Author Disclosures: R.A. Thandavarayan: None. D. Joladarashi: None. S. Suresh Babu: None. P. Jeyabal: None. S. Krishnamurthy: None. V.N. Garikipati: None. S.K. Verma: None. R. Kishore: None. P. Krishnamurthy: None.
- © 2015 by American Heart Association, Inc.