Inhibition of type i collagen expression by antisense oligonucleotides in keloid fibroblast cultures Academic Article uri icon

abstract

  • Keloid is a prototypic fibrotic disease characterized hy elevated type I collagen mRNA level and excess production of collagen. Antisense oligonucleotides (ASOs) were used to target various exon and intron sequences of the pro-al(I) type I collagen. Western analysis employing antibodies specific for fibronectin and the C-terminal propeptide of type I collagen (LF41) was conducted to detect alterations in type I collagen. Quantitation of type I collagen was normalized with corresponding fibronectin levels. The percent inhibition was variable, ranging from 6% to 74% depending upon the sequence targeted. For instance, an ASO specific for intron 46 had no inhibitory effect, whereas those specific for exon sequences, such as exons 2, 50, 51, and 52, suppressed type I collagen, 33% to 74% relative to the control. Consistent with previous findings in mouse 3T3 fibroblasts (Laptev et al. Biochem. 33:11033, 1994), the most effective ASOs were those targeted to sequences that were predicted to form double-stranded structures in RNA transcripts. Thus, ASOs that demonstrate relatively high reduction of type I collagen expression may be effective in inhibiting collagen synthesis by fibroblasts in the keloid.

published proceedings

  • Journal of Investigative Medicine

author list (cited authors)

  • Laptev, A., Li, S. U., Rouda, S., Qin, H., Kennedy, S. H., Prockop, D. J., & Tan, E.

complete list of authors

  • Laptev, A||Li, SU||Rouda, S||Qin, H||Kennedy, SH||Prockop, DJ||Tan, E

publication date

  • January 1996