The effects of social isolation on wound healing mechanisms in female mice.
Various stressors impair wound healing in humans and rodents. For example, social isolation delays wound closure in rodents, but the healing mechanisms that underlie this delay have yet to be identified. Here, the effects of three weeks of social isolation on hypothalamic-pituitary-adrenal axis responses and healing factors involved in the inflammatory and proliferative phases of wound healing were assessed in adult female hairless mice. Social isolation reduced basal circulating corticosterone concentrations and increased body and thymus weights compared with group-housed controls. Isolation impaired dermal wound closure by up to 30% and reduced initial total wound bacterial load relative to controls. Inflammatory gene expression in the wounds was not affected by the observed differences in wound bacterial load. However, isolation reduced wound gene expression of keratinocyte growth factor and vascular endothelial growth factor, which are involved in keratinocyte proliferation/migration and angiogenesis during the proliferative phase of healing. These data indicate that social isolation induces healing impairments that may be attributed to reductions in growth factors necessary for proper skin cell proliferation and blood vessel growth during healing. This healing impairment occurred in the absence of both high wound bacterial load and elevated circulating glucocorticoids, which have previously been hypothesized to be required for stress-impaired healing in mice.
Department of Periodontics, College of Dentistry, University of Illinois at Chicago (UIC), Chicago, IL 60612, USA; Center for Wound Healing and Tissue Regeneration, College of Dentistry, UIC, Chicago, IL 60612, USA.
Leah M
LM
Pyter
Department of Oral Medicine, The Affiliated Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Linglan
L
Yang
Section of Periodontology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
José M
JM
da Rocha
Department of Periodontics, College of Dentistry, University of Illinois at Chicago (UIC), Chicago, IL 60612, USA; Center for Wound Healing and Tissue Regeneration, College of Dentistry, UIC, Chicago, IL 60612, USA; Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA 16802, USA; College of Nursing, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: cge2@psu.edu.
Christopher G
CG
Engeland
D000818:Animals; D058491:Bacterial Load; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D015870:Gene Expression; D006799:Housing, Animal; D051379:Mice; D008812:Mice, Hairless; D009929:Organ Size; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000293:injuries* / Q000382:microbiology; D012934:Social Isolation; D013950:Thymus Gland / Q000502:physiology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D051523:Fibroblast Growth Factor 7; D003345:Corticosterone
Bacteria; Glucocorticoids; Growth factors; Inflammation; Stress; Tissue repair