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A sense phosphorothioate oligodeoxynucleotide containing the transforming growth factor beta regulatory element acts as a novel local nonsteroidal antifibrotic drug
Author(s) -
Cutroneo Kenneth R
Publication year - 2000
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2000.00399.x
Subject(s) - oligonucleotide , fibrosis , transforming growth factor , pharmacology , transforming growth factor beta , chemistry , growth factor , biology , microbiology and biotechnology , biochemistry , medicine , dna , receptor
Fibrosis is a potential response to tissue injury. At present, glucocorticoids with their numerous toxic side effects are the only effective treatment for fibrotic diseases. Granulomas induced by sponge implantation were treated with single‐stranded phosphorothioate oligodeoxynucleotides containing the wild type or mutated transforming growth factor‐β response element designed to inhibit the rat proα1(I) promoter activity. Single‐stranded phosphorothioate oligonucleotides resulted in antifibrotic activity based on their ability to reduce granuloma tissue formation and selectively inhibit collagen synthesis. The mutated single‐standed phosphorothioate oligonucleotides or dexamethasone given at an equivalent dose to single‐standed phosphorothioate oligonucleotides failed to do so. These data suggest that the phosphorothioate oligodeoxynucleotide containing the transforming growth factor‐β regulatory element has an antifibrotic effect and may be used to inhibit the development of fibrosis.