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[follistatin-related gene] This is also known as follistatin-like-3 (abbr. FSTL3). The human gene encoding FLRG encodes a secreted glycoprotein of 263 amino acids that displays 85 % amino acid identity with the mouse gene. The gene is expressed in placenta, amniocytes, chorionic villi, and bone marrow stromal cells. Weak expression is observed in fibroblasts, keratinocytes, and endothelial cells (Hayette et al, 1998). Expression can be induced by TGF-beta (Bartholin et al, 2001). FLRG and activin A are expressed in the same hematopoietic cells and regulated by TGF-beta, suggesting a role in hematopoiesis. FLRG is capable of binding to activin A (Maguer-Satta, 2001) and binds to Activin B with lower potency (Schneyer et al, 2003). Activin A is an inducer of FLRG expression and FLRG regulates its own activin A induced expression (Bartholin et al, 2002).

Wankell et al (2001) have reported that FLRG mRNA expression is induced in keratinocytes by KGF, EGF and TGF-beta-1, and in fibroblasts by PDGF and EGF. The protein is expressed during wound healing but its distribution within the wound is different from that of follistatin.

Ciarmela et al (2003) have reported that the protein is expressed by human trophoblasts, epithelial amniotic and chorionic cells and maternal decidua.

Tortoriello et al (2001) have reported that FLRG is expressed ubiquitously in human adult and fetal tissues. While most cells express FLRG mRNA, only a minority of the cultures secrete the protein and the protein appears to have a nuclear localization.

Hill et al (2002) have reported that FLRG is part of a latent complex of circulating myostatin (GDF8).

Tsuchida et al (2000) have reported that the protein binds to activin A and BMP2 and that it interferes with BMP2 cell signaling. Maguer-Satta et al (2003) have reported that FLRG downmodulates the effects of activin A and BMP2 on erythroid maturation.

Zhang et al (2003) have reported that FLRG is secreted from rat astroglial cells and may play a role in the regulation of activin A in brain wound healing in response to TGF-beta-1.

Xia et al (2004) have demonstrated that FLRG is likely to be a local regulator of activin A action in gonadal development and gametogenesis as overexpression of this protein in the gonads of transgenic mice causes defects in gonadal development and function.

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