# The evaluation of the effect of estrogen administration on cutaneous wound healing in Staphylococcus aureus-infected diabetic and nondiabetic mice

**Authors:** Kanae Mukai, Kohei Ogura, Yukari Nakajima, Toshio Nakatani

PMC · DOI: 10.1371/journal.pone.0339341 · PLOS One · 2025-12-30

## TL;DR

This study examines how estrogen affects wound healing in diabetic and nondiabetic mice infected with Staphylococcus aureus.

## Contribution

The study reveals that estrogen improves wound healing in nondiabetic mice infected with S. aureus by modulating immune responses and lymphatic vessel formation.

## Key findings

- S. aureus infection delays wound healing in diabetic mice by causing inflammation and inhibiting collagen and vessel formation.
- Estrogen administration in nondiabetic mice reduces macrophage numbers and increases lymphatic vessels in infected wounds.
- Estrogen does not reverse the negative effects of S. aureus infection in diabetic wounds.

## Abstract

Diabetes-related infection has become a difficult and significant global public health issue. Estrogen has specific hormones that promote cutaneous wounds in diabetic mice. However, the impact of estrogen on skin-colonized pathogenic bacteria is unknown. The purpose of this study was to look into how estrogen affects wounds infected with Staphylococcus aureus. Nondiabetic db/ + mice and diabetic db/db mice were both injured, and bacterial suspension was applied to each wound site. Estrogen or vehicles were injected intraperitoneally every 3–4 days after wounding. S. aureus infection impaired diabetic wounds and reduced collagen deposition. Immunostaining revealed that S. aureus infection reduced the number of blood and lymphatic vessels while increasing the number of neutrophils in nondiabetic wounds, regardless of estrogen treatment. Conversely, estrogen administration reduced the number of macrophages in S. aureus-infected nondiabetic wounds compared to vehicle-treated wounds. The number of lymphatic vessels was roughly double that of estrogen administration in S. aureus-infected nondiabetic wounds. Our findings showed that S. aureus infection in diabetic wounds delayed cutaneous wound healing due to excessive inflammation, inhibited collagen deposition, and impaired angiogenesis or lymphangiogenesis, although estrogen administration did not reverse these effects. Our findings also revealed that estrogen administration effectively treated S. aureus-infected nondiabetic wounds by regulating the immune response and increasing the synthesis of lymphatic vessels.

## Linked entities

- **Chemicals:** estrogen (PubChem CID 12115739)
- **Diseases:** diabetes (MONDO:0005015), Staphylococcus aureus infection (MONDO:0005545)

## Full-text entities

- **Diseases:** Diabetes (MESH:D003920), infected (MESH:D007239), inflammation (MESH:D007249), wounds infected (MESH:D014946)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Staphylococcus aureus (species) [taxon 1280]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12962825/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12962825/full.md

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Source: https://tomesphere.com/paper/PMC12962825