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


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


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).

Author information




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).

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