Tohoku J. Exp. Med., 2005, 207(1)

Fibrin Stimulates the Proliferation of Human Keratinocytes through the Autocrine Mechanism of Transforming Growth Factor-α and Epidermal Growth Factor Receptor

MISA YAMAMOTO, HIROKO YANAGA,² HIROMICHI NISHINA,² SHOJI WATABE and KOICHI MAMBA¹

Faculty of Health Sciences, Yamaguchi University School of Medicine, Yamaguchi, Japan, ¹United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan, and ²Yanaga Clinic and Tissue Culture Laboratory, Kitakyusyu, Japan

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)-α, 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-α and epidermal growth factor. The keratinocytes increased dramatically in their number, and the TGF-α 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-α, 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-α/EGF-R pathway.

keywords ——fibrin; keratinocytes; TGF-α; EGF-R; wound healing

© 2005 Tohoku University Medical Press

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Correspondence: Misa Yamamoto, MT (Medical Technologist), CT (Cytologist), Faculty of Health Sciences, Yamaguchi University School of Medicine, Minami- Kogushi 1-1-1, Ube, Yamaguchi, 755-8554, Japan.

e-mail: yamamoms@yamaguchi-u.ac.jp