title: 17beta-estradiol regulates the secretion of TGF-beta by cultured human dermal fibroblasts.
abstract: Estrogen plays an important role in skin homeostasis, as demonstrated by the changes seen in the skin of post-menopausal women, changes reversed by HRT. Estrogen also has a role in wound healing, since estrogen deficiency as occurs post-menopausally and in ovariectomised animals, is associated with a reduced rate of wound healing. Estrogen appears to modulate all phases of wound healing with effects on inflammatory cells, epithelialization, angiogenesis, extracellular matrix deposition and tissue remodelling. This study was designed to investigate the effects of 17beta-estradiol on cultured human dermal fibroblasts using an in vitro wound-healing assay. The end points investigated were cell migration, proliferation, total collagen secretion and active TGF-beta1 secretion. 17beta-estradiol significantly increased the migration and proliferation of cultured dermal fibroblasts following mechanical wounding, although the secretion of total soluble collagen was not altered. An increase in TGF-beta1 was demonstrated by unwounded confluent dermal fibroblast monolayers in response to 17beta-estradiol, but paradoxically, a decrease in the secretion of TGF-beta1 was demonstrated in the mechanically wounded dermal fibroblasts. These results identify human dermal fibroblasts as estrogen target cells and provide further evidence for a role by which estrogen regulates this particular cell type as part of the wound-healing process. However, the paradoxical nature of the effect of estrogen on TGF-beta1 secretion following mechanical wounding suggests that the cellular mechanism of action is complex. A greater understanding of the cell-specific action of estrogen may help to develop therapies that will improve cutaneous wound healing in the future.
authors.affiliation: Burns & Plastic Surgery Research Unit, Medical Biosciences, School of Life Sciences, University of Bradford, Richmond Road, Bradford, West Yorkshire, UK.
authors.forename: S
authors.initials: S
authors.lastname: Stevenson
authors.forename: L D
authors.initials: LD
authors.lastname: Nelson
authors.forename: D T
authors.initials: DT
authors.lastname: Sharpe
authors.forename: M J
authors.initials: MJ
authors.lastname: Thornton
mesh_terms: D001672:Biocompatible Materials; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000166:cytology*; D004958:Estradiol / Q000502:physiology*; D004967:Estrogens / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing
chemical_list: D001672:Biocompatible Materials; D004967:Estrogens; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D016685:Mitomycin; D003094:Collagen