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Genome-wide screening of m6A profiling of cutaneous wound healing in diabetic mice

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Abstract

Objective

Impaired wound healing in diabetes mellitus (DM) is a major health burden on patients, their families, and society. The present study aimed to systematically profile the m6A modification landscape in cutaneous wounds in a diabetic mouse model.

Approach

Diabetes was induced in mice through a single intraperitoneal injection of streptozotocin (STZ); a single intraperitoneal injection of PBS was made in control mice for comparisons. Both groups then received an 8-mm diameter, full-thickness dorsal body wound with a biopsy punch. Five days after wound surgery, western blot analysis of harvested wound tissues from both groups was used to assess the expression of m6A-related enzymes. Genome-wide profiling of m6A-tagged transcripts was performed through MeRIP-seq and RNA-seq.

Results

ALKBH5, an m6A eraser, was significantly upregulated, while METTL3, METTL14, and WTAP, m6A writers, were markedly downregulated in the diabetic wounds. Additionally, a total of 1335 m6A peaks were differentially expressed in MeRIP-seq and RNA-seq analyses, with 558 upregulated and 777 downregulated peaks. Finally, there was hypomethylated and hypermethylated differentiation at the gene and transcript levels.

Innovation

The present study was the first to reveal the m6A landscape in diabetic wounds in an animal model.

Conclusion

This study, by deeply analyzing the role of m6A modifications in diabetic wound healing, provides new insights and understanding into the molecular mechanisms of diabetic wound healing. Future research could further explore how m6A modifications regulate the wound healing process, thereby offering new potential targets for the treatment of diabetic wounds.

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Notes

  1. Note: (FPKM = [total_exon_fragments/mapped_reads(millions) × exon_length(kB)]).

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Funding

Sponsorship for this study and article processing charges were supported by a Grant from the Shanghai Municipal Health Commission (No. 20204Y0430).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital, JiaoTong University, Shanghai, China

    Junjie Shen, Hua Chen & Jiezhi Dai

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  1. Junjie Shen
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  2. Hua Chen
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Contributions

Conceptualization, JZD; Investigation, JJS; Methodology, JJS and HC; Writing—original draft, JJS; Writing—review and editing, JZD. All authors have read and approved the manuscript for publication.

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Correspondence to Hua Chen or Jiezhi Dai.

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The authors have no relevant financial or non-financial interests to disclose.

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Experiments and procedures involving laboratory mice were approved by the Animal Care and Use Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital.

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Shen, J., Chen, H. & Dai, J. Genome-wide screening of m6A profiling of cutaneous wound healing in diabetic mice. Mol Biol Rep 51, 175 (2024). https://doi.org/10.1007/s11033-023-09089-7

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