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Blockade of Glucocorticoid Receptors Improves Cutaneous Wound Healing in Stressed Mice
Author(s) -
Almeida Taís,
Pires Taiza,
Costa Andrea
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.876.2
Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation and remodeling and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic–pituitary–adrenal axis (HPA) and the glucocorticoids (GC) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress whereas control animals were not subjected to stress. These stressed and control animals were treated with RU486 (20mg/Kg) every day. A full‐thickness excisional lesion was generated, and 7 days later lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486‐treated in comparison to non‐treated mice and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals.The Stress+RU486 group showed a decrease in inflammatory cell infiltration, and in hypoxia‐inducible factor 1‐alpha(HIF 1‐α) and inducible nitric oxide‐synthase (NOS2) expression meanwhile there was an increase in myofibroblasts.Measurement Groups Granulation tissue (S) Granulation tissue (D) Granulation tissue (total) Neutrophils/mm 2 Control 853 ± 140 344 ± 71 637 ± 99 RU486 1402 ± 176 132 ± 60 *# 767 ± 56 Stress 967 ± 62 566 ± 53 * 792 ± 46 * Stress+RU486 921 ± 54 202 ± 50 # 598 ± 52 # F4/80‐positive macrophages/mm 2 Control 153 ± 32 567 ± 43 360 ± 35 RU486 209 ± 35 # 640 ± 49 421 ± 36 Stress 423 ± 37 * 598 ± 45 505 ± 30 * Stress+RU486 80 ± 17 # 262 ± 35 *# 169 ± 21 *# a‐SMA positive myofibroblasts/mm 2 Control 350 ± 41 * 25 ± 12 196 ± 29 RU486 141 ± 27 15 ± 11 81 ± 17 * Stress 157 ± 27 * 38 ± 11 102 ± 16 * Stress+RU486 257 ± 39 # 59 ± 16 161 ± 24 Data shown as mean ± SEM. S=Superficial region, D=Deep region; * vs Control group; # vs Stress group.In conclusion, blockade of GC receptors with RU486 partially ameliorates stress‐impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway.