Transforming growth factor-β1: Regulation with a TGF-β1 antisense oligomer
Transforming growth factor-β1 (TGF-β1) is a member of a family of polypeptides important in embryogenesis, tissue repair and cell growth. On the other hand, TGF-β1 is considered to be a causative factor in organ dysfunction and in immune deregulation of AIDS. The proteoglycan decorin and anti-TGF-β antibodies have been used to mitigate the adverse consequences of TGF-β1 overexpression. We describe here a novel TGF-β1 complementary DNA (antisense oligomer) that is specific for TGF-β1 genomic DNA. The TGF-β1 antisense oligomer, complementary to the nucleotides flanking the first transcription start site of the human TGF-β1 gene and phosphorothioate modified, was efficacious in: (a) constraining TGF-β1 promoter activity; (b) reducing TGF-β1 secretion; (c) preventing TGF-β1 dependent inhibition of DNA synthesis; and (d) inhibiting phenotypic alterations in TGF-β1 sensitive A-549 human adenocarcinoma cells. Our findings, in addition to demonstrating the efficacy of the TGF-β1 antisense oligomer, suggest that the oligomer might be of value for the treatment of diseases in which TGF-β1 overexpression might play a pathogenetic role.