title: Fibrin stimulates the proliferation of human keratinocytes through the autocrine mechanism of transforming growth factor-alpha and epidermal growth factor receptor.
abstract: In the field of dermatology and plastic and reconstructive surgery, fibrin gel is regarded as a material that promotes wound healing. To test the hypothesis that fibrin may promote the growth of the epidermis, we examined its effects on the proliferation of cultured keratinocytes. Human keratinocytes were cultivated in fibrin-coated wells, and the cell numbers and transforming growth factor (TGF)-alpha, secreted into the cultured medium, were measured. We also assessed the capacity of epidermal growth factor receptor (EGF-R) that is responsible for all known actions of TGF-alpha and epidermal growth factor. The keratinocytes increased dramatically in their number, and the TGF-alpha secretion and the binding capacity of EGF-R were also increased dramatically in the presence of fibrin. These findings suggest that fibrin supports the proliferation of keratinocytes in an autocrine fashion via EGF-R; namely, fibrin stimulates keratinocytes to secrete TGF-alpha, which in turn increases cell proliferation and EGF-R capacity. We propose that fibrin can support the wound healing process of the epidermis via the TGF-alpha/EGF-R pathway.
authors.affiliation: Faculty of Health Sciences, Yamaguchi University School of Medicine,Yamaguchi, Japan. yamamoms@yamaguchi-u.ac.jp
authors.forename: Misa
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yanaga
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nishina
authors.forename: Shoji
authors.initials: S
authors.lastname: Watabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Mamba
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D003470:Culture Media; D016207:Cytokines; D016211:Transforming Growth Factor alpha; D005337:Fibrin; D066246:ErbB Receptors