Immunolocalization of fibroblast growth factor receptors in normal and wounded human skin

Fibroblast growth factors (FGFs) have been shown to play diverse roles in various tissues. To define their sites of action in normal human skin and during wound healing, we determined the protein expression of the four known fibroblast growth factor receptors (FGFRs) in normal and wounded human skin by immunohistochemistry. Four receptors (FGFR-1 to FGFR-4) showed distinct patterns of expression in normal skin. Expression of FGFR-1 was widespread in the epidermis, appendages, arrector pili muscles, blood vessels, and dermal fibroblasts. Intense expression of FGFR-2 and FGFR-4 was seen in the arrector pili muscles and smooth muscle cells of vessels. In the epidermis, the basal layer showed immunoreactivity for FGFR-2, whereas the suprabasal layers and the inner layers of hair follicles showed strong immunoreactivity for FGFR-3. In wounded skin, there was strong expression of FGFR-1 and FGFR-3, and moderate expression of FGFR-2 and FGFR-4 in the basal layer in newly forming epidermis. In granulation tissues, neocapillaries expressed all four FGFRs, fibroblasts/myofibroblasts expressed FGFR-1 and FGFR-3, and mononuclear inflammatory cells expressed FGFR-1 and FGFR-3. Our results suggest that the differences in the spatial patterns of FGFR expression in normal skin may generate functional diversity in response to FGFs and that in wounded skin, FGFs may function in wound healing via the induced FGFRs.