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Resveratrol promotes skin wound healing by regulating the miR-212/CASP8 axis

Abstract

The wound-healing process is a natural response to burn injury. Resveratrol (RES) may have potential as a therapy for wound healing, but how and whether RES regulates skin repair remains poorly understood. Human epidermal keratinocyte (HaCaT) cells were treated with lipopolysaccharide (LPS), and a mouse skin wound-healing model was established. Cell viability and apoptosis were analyzed by 3-(4,5-dimethyl-2-thiazolyl)−2,5-diphenyl-2-H-tetrazolium bromide or flow cytometry. Cell proliferation was assessed by cell viability and colony-formation analyses. Cell migration was tested by wound-healing analysis. The microRNA-212 (miR-212) and caspase-8 (CASP8) levels were determined by quantitative reverse transcription polymerase chain reaction and western blotting. The correlation between miR-212 and CASP8 was analyzed by dual-luciferase reporter analysis. Skin wound healing in mice was assessed by measuring the wound area and gap after hematoxylin–eosin (HE) staining. RES reduced the LPS-induced reduction in viability and apoptosis in HaCaT cells. miR-212 expression was reduced by LPS and increased by exposure to RES. RES promoted cell proliferation and migration after LPS treatment by increasing miR-212 levels. CASP8 was a target of miR-212. CASP8 silencing promoted cell proliferation and migration, which was reversed by miR-212 knockdown in LPS-treated HaCaT cells. RES promoted skin wound healing in mice, which was reduced by miR-212 knockdown. Thus, RES facilitates cell proliferation and migration in LPS-treated HaCaT cells and promotes skin wound-healing in a mouse model by regulating the miR-212/CASP8 axis.

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Fig. 1: The influence of RES on LPS-induced injury.
Fig. 2: The influence of miR-212 and RES on cell proliferation and migration.
Fig. 3: The relationship between miR-212 and CASP8.
Fig. 4: The influence of miR-212 and CASP8 on cell proliferation and migration.
Fig. 5: The influence of RES and miR-212 on wound healing in mice.

Data availability

All data generated or analyzed during this study are included in this article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by Natural Science Fund Project of Inner Mongolia autonomous region (2018BS08009); Inner Mongolia Medical University Science and Technology Million Project (YKD2017KJBW016), and Natural Science Foundation of Hunan Province (2020JJ5861).

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Conception and study design: Y. L.; Data acquisition: W. X.; Data analysis: C.-W. W., J.-P. S.; Paper drafting: Z.-Q. S.; Paper revising: J.-D. Z.

Corresponding author

Correspondence to Jian-Da Zhou.

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The animal experiments were approved via the Animal Ethical Committee of The Third Xiangya Hospital and conducted in line with the National Institutes of Health.

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Liu, Y., Xiong, W., Wang, CW. et al. Resveratrol promotes skin wound healing by regulating the miR-212/CASP8 axis. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00621-6

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