Transforming growth factor-beta 1: regulation with a TGF-beta 1 antisense oligomer

Transforming growth factor-beta 1 (TGF-beta 1) is a member of a family of polypeptides important in embroygenesis, tissue repair and cell growth. On the other hand, TGF-beta 1 is considered to be a causative factor in organ dysfunction and in immune deregulation of AIDS. The proteoglycan decorin and anti-TGF-beta antibodies have been used to mitigate the adverse consequences of TGF-beta 1 overexpression. We describe here a novel TGF-beta 1 complementary DNA (antisense oligomer) that is specific for TGF-beta 1 genomic DNA. The TGF-beta 1 antisense oligomer, complementary to the nucleotides flanking the first transcription start site of the human TGF-beta 1 gene and phosphorothioate modified, was efficacious in: (a) constraining TGF-beta 1 promoter activity; (b) reducing TGF-beta 1 secretion; (c) preventing TGF-beta 1 dependent inhibition of DNA synthesis; and (d) inhibiting phenotypic alterations in TGF-beta sensitive A-549 human adenocarcinoma cells. Our findings, in addition to demonstrating the efficacy of the TGF-beta 1 antisense oligomer, suggest that the oligomer might be of value for the treatment of diseases in which TGF-beta 1 overexpression might play a pathogenetic role.