The effect of 17β-estradiol on cutaneous wound healing in protein-malnourished ovariectomized female mouse model

PLoS One. 2014 Dec 17;9(12):e115564. doi: 10.1371/journal.pone.0115564. eCollection 2014.

Abstract

Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Diet, Protein-Restricted
  • Disease Models, Animal*
  • Estradiol / pharmacology*
  • Estrogens / pharmacology
  • Female
  • Immunoenzyme Techniques
  • Kwashiorkor / drug therapy*
  • Kwashiorkor / etiology
  • Kwashiorkor / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Ovariectomy / adverse effects*
  • Skin / drug effects*
  • Skin / injuries
  • Skin / pathology
  • Wound Healing / drug effects*

Substances

  • Estrogens
  • Estradiol

Grants and funding

All of this work was supported by JSPS KAKENHI (Grant Number 25293430 to T. Nakatani) and research funding from Kanazawa University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.