TGF-beta1-dependent differential expression of a rat homolog for latent TGF-beta binding protein in astrocytes and C6 glioma cells.
Transforming growth factor-beta1 (TGF-beta1) is widely recognized for its multiple roles in development, cellular maintenance, and protection against injury. In the brain, TGF-beta1 upregulation in microglia/macrophages is a predominant response to lesion and during pathology. However, the precise functions of TGF-beta1 in this context are still enigmatic. The present study investigates changes in astroglial gene expression as a major target of TGF-beta1 signaling in the brain. Differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used to identify several gene fragments differentially regulated by TGF-beta1 in rat astrocytes and C6 glioma cells. Among the cDNAs regulated by TGF-beta1 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-2 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-1 might lead to self-activation and exaggeration of TGF-beta signaling. These data will extend our current understanding of TGF-beta1 functioning on lesion-related features of glial cells.
Department of Anatomy and Cell Biology III, University of Heidelberg, Germany. krok@server3.medizin.uni-leipzig.de
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D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation
D002352:Carrier Proteins; D018076:DNA, Complementary; D053779:Latent TGF-beta Binding Proteins; C509037:Ltbp2 protein, rat; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta