Follistatin is a secreted
protein that binds
activin in vitro and in vivo and thereby inhibits its
biological functions. Recently, related human and murine genes, designated
follistatin-related gene (FLRG), were identified, and their products were shown to bind
activin with high affinity. In this study we further characterized the murine
FLRG protein, and we analyzed its tissue-specific expression and regulation in comparison with those of
follistatin. Transient expression of the mouse
FLRG protein in COS-1 cells revealed that the FLRG
cDNA encodes a secreted
glycoprotein. FLRG
mRNA was expressed at high levels in the lung, the testis, the uterus and, particularly, the skin. Immunohistochemistry revealed the presence of FLRG in the basement membrane between the dermis and the epidermis and around blood vessels. FLRG
mRNA expression was induced in keratinocytes by
keratinocyte growth factor,
epidermal growth factor and
transforming growth factor-beta 1, and in fibroblasts by
platelet-derived growth factor and
epidermal growth factor. The induction was more rapid, but weaker, than that of
follistatin. Most interestingly, both
follistatin and FLRG were expressed during the wound healing process, but their distribution within the
wound was different. The different expression pattern of FLRG and
follistatin and their differential regulation suggest different functions of these
activin-
binding proteins in vivo.