Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice.

Autor: Xue TT; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China., Cha HJ; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China., Liu QK; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China., Yang D; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China., Zhang Z; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China., Jiang JS; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China., Song JK; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China., Wang MX; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China., Shen F; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China., Zheng Q; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China., Kuai L; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China., Ru Y; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. Electronic address: pansy022@hotmail.com., Li X; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: 13661956326@163.com., Li B; Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: 18930568129@163.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Sep 24; Vol. 726, pp. 150235. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1016/j.bbrc.2024.150235
Abstrakt: 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 SIRT6 flox/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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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