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Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair, glycolysis and inflammation. However, the role of sirtuin 6 (<jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6), a <jats:styled-content style=\"fixed-case\">NAD<\/jats:styled-content>+\u2010dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyse the role of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6 in cutaneous wound healing, paired 6\u2010mm stented wound was created in diabetic db\/db mice and injected si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> against <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6 in the wound margins (transfection agent alone and nonsense si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6\u2010si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010treated diabetic wound showed impaired healing, which was associated with reduced capillary density (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>31\u2010staining vessels) when compared to control treatment. Interestingly, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6 deficiency decreased vascular endothelial growth factor expression and proliferation markers in the wounds. Furthermore, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6 ablation in diabetic wound promotes nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule\u20101, vascular cell adhesion molecule\u20101, tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> and interleukin\u20101<jats:italic>\u03b2<\/jats:italic>) and increased oxidative stress. Collectively, our findings demonstrate that loss of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6 in cutaneous wound aggravates proinflammatory response by increasing <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that the activation of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>6 signalling might be a potential therapeutic approach for promoting wound healing in diabetics.<\/jats:p>","DOI":"10.1111\/exd.12762","type":"journal-article","created":{"date-parts":[[2015,5,23]],"date-time":"2015-05-23T07:04:09Z","timestamp":1432364649000},"page":"773-778","source":"Crossref","is-referenced-by-count":47,"title":["Sirtuin\u20106 deficiency exacerbates diabetes\u2010induced impairment of wound healing"],"prefix":"10.1111","volume":"24","author":[{"given":"Rajarajan A.","family":"Thandavarayan","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences Center for Cardiovascular Regeneration Houston Methodist Research Institute Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata Naga Srikanth","family":"Garikipati","sequence":"additional","affiliation":[{"name":"Center for 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