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Updated: May 13, 2026
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice
Ting-Ting Xue1, Hui-Jung Cha1, Qing-Kai Liu1
1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Background:
Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear.
Methods:
We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration.
Results:
Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1β, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice.
Conclusions:
SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.
Insights
Sirtuin-6 (SIRT6) is crucial for diabetic ulcer (DU) healing. Loss of SIRT6 impairs wound repair by increasing inflammation and reducing re-epithelialization, suggesting SIRT6 agonists may treat DUs.
Area of Science:
- Biomedical Science
- Epigenetics
- Wound Healing Research
Background:
- Diabetic ulcers (DUs) present a significant clinical challenge due to chronic inflammation and delayed healing.
- Current treatments for refractory DUs are varied, with optimal strategies remaining debated.
- Sirtuin-6 (SIRT6), an epigenetic regulator, has known roles in inflammation and proliferation, but its specific function in DUs is not well understood.
Purpose of the Study:
- To investigate the role of Sirtuin-6 (SIRT6) in the healing process of diabetic ulcers (DUs).
- To assess the therapeutic potential of targeting SIRT6 for DU treatment.
Main Methods:
- Generated tamoxifen-inducible SIRT6 knockout mice to study SIRT6's function in DUs.
- Analyzed gene and protein expression of SIRT6 and inflammatory markers using Western blotting and RT-qPCR.
- Performed histopathological examinations to evaluate re-epithelialization, inflammation, and angiogenesis markers.
Main Results:
- SIRT6 knockout significantly inhibited diabetic ulcer healing.
- Loss of SIRT6 led to attenuated re-epithelialization and exacerbated inflammatory responses.
- Impaired angiogenesis was observed in SIRT6-deficient diabetic ulcers.
Conclusions:
- SIRT6 plays a vital role in promoting diabetic ulcer healing by enhancing epidermal proliferation, regulating inflammation, and improving angiogenesis.
- Targeting SIRT6 with agonists presents a promising therapeutic strategy for treating diabetic ulcers.
