TGF-β1-dependent differential expression of a rat homolog for latent TGF-β binding protein in astrocytes and C6 glioma cells

Transforming growth factor-beta 1 (TGF-beta 1) is widely recognized for its multiple roles in development, cellular maintenance, and protection against injury. In the brain, TGF-beta 1 upregulation in microglia/macrophages is a predominant response to lesion and during pathology However, the precise functions of TGF-beta 1 in this context are still enigmatic. The present study investigates changes in astroglial gene expression as a major target of TGF-beta 1 signaling in the brain. Differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used to identify several gene fragments differentially regulated by TGF-beta 1 in rat astrocytes and C6 glioma cells. Among the cDNAs regulated by TGF-beta 1 in C6 cells two cDNAs showed homology to alpha-tropomyosin and glycerol-3-phosphate dehydrogenase, respectively. Cloning of a full length cDNA corresponding to a differentially regulated gene fragment revealed close homology to latent TGF-beta binding protein (LTBP)-2. Data using antisense LTBP-2 oligonucleotides to decrease LTBP-2 expression suggest that LTBP-8 functions to activate TGF-beta. Therefore, it is likely that upregulation of the rat LTBP-2 homolog mRNA in C6 cells and cortical astrocytes by TGF-beta 1 might lead to self-activation and exaggeration of TGF-beta signaling. These data will extend our current understanding of TGF-beta 1 functioning on lesion-related features of glial cells. (C) 1999 Wiley-Liss, Inc.