Sirtuins as therapeutic targets for improving delayed wound healing in diabetes

Abstract

Sirtuins are a vast family of histone deacetylases, which are NAD⁺ dependent enzymes, consisting of seven members, namely SIRT 1, SIRT 6 and SIRT 7 located within the nucleus, SIRT 2 in the cytoplasm and SIRT 3, SIRT 4 and SIRT 5 in the mitochondria. They have vital roles in regulating various biological functions such as age-related metabolic disorders, inflammation, stress response, cardiovascular and neuronal functions. Delayed wound healing is one of the complication of diabetes, which can lead to lower limb amputation if not treated timely. SIRT 1, 3 and 6 are potent targets for diabetic wound healing. SIRT 1 deficiency reduces recruitment of fibroblasts, macrophages, mast cells, neutrophils to wound site and delays wound healing; negatively expressing MMP-9. The SIRT 1 mediated signalling pathway in diabetic wound healing is the SIRT 1–FOXO–c-Myc pathway. On the contrary, SIRT 3 deficiency impairs proliferation and migration of fibroblasts and SIRT 6 deficiency impairs wound closure rate and interrupts the vascular remodelling. This review focuses on the role of sirtuins in improving delayed wound healing in diabetes and its natural modulators with their specific functions towards healing diabetic wounds.

Keywords:

• Sirtuins
• diabetic wound healing
• fibroblasts
• keratinocytes
• macrophages

Acknowledgement

Authors are thankful to Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, India.

Author contributions

Conceptualisation: RS and FB; investigation: FB; original draft preparation: FB; figures: APV; tables: DKP; FaB review and editing: RS, KN, APV and KG; supervision: RS and KN.

Disclosure statement

Authors declared no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.