Regulation of FLRG expression in rat primary astroglial cells and injured brain tissue by transforming growth factor-β1 (TGF-β1)

Follistatin-related gene (FLRG) is a member of the follistatin family of proteins and interacts with transforming growth factor (TGF) superfamily proteins like follistatin. To understand the expression level of FLRG in brain tissue, we examined whether primary neurons and glial cells from rat embryos express FLRG mRNA and produce its protein product. FLRG and follistain mRNAs were mainly expressed in astroglial cells, while activin A mRNA was abundant in primary neurons. TGF-beta1 highly enhanced expression levels of FLRG mRNA in astroglial cells, compared with those of follistatin and activin A mRNAs. Particularly, TGF-beta1 facilitated the secretion of FLRG protein from primary astroglial cells in a dose-dependent manner. Moreover, changes in expression levels of FLRG mRNA and protein in brain tissue were also analyzed after a penetrating injury, using quantitative polymerase chain reactin (PCR) and immunohistochemical methods. Expression levels of FLRG mRNA were significantly increased in damaged regions after penetrating injury together with those of activin A and TGF-beta1 mRNAs. Immunohistochemical observations showed that positive signals of FLRG protein were colocalized in glial fibrillary acidic protei n-positive reactive astroglial cells located in damaged regions after a penetrating injury. The expression of follistatin mRNA rather decreased in damage regions after the brain injury. These results suggest that FLRG is synthesized in and secreted from astroglial cells. In particular, FLRG, but not follistatin, may play a role in the regulation of activin A in brain wound healing in response to TGF-beta1. (C) 2003 Wiley-Liss, Inc.