Regulation of transforming growth factor-β1 (TGF-β1) expression with a novel TGF-β1 complementary DNA
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; and c) preventing TGF-beta 1 dependent inhibition of DNA synthesis in TGF-beta sensitive A-549 human adenocarcinoma cells. The biologic activities of the TGF-beta 1 antisense oligomer were sequence specific since neither the TGF-beta 1 sense oligomer nor the TGF-beta 1 missense oligomer prevented TGF-beta 1 expression. Our findings, in addition to demonstrating the efficacy and specificity 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 (e.g., diabetic renal disease, AIDS).