The Laryngoscope · 2014
Smad3: an emerging target for vocal fold fibrosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Paul Benjamin C, Rafii Benjamin Y, Gandonu Sonate, Bing Renjie, Born Hayley, Amin Milan R, Branski Ryan C
Аннотация
OBJECTIVES/HYPOTHESIS: To determine the efficacy of small interfering RNA (siRNA) targeting Smad3 to mediate fibroplasia in vitro, to investigate the temporal regulation of Smad3 following vocal fold (VF) injury, and to determine the local and distal effects of Smad3 siRNA VF injection.
STUDY DESIGN: In vitro and in vivo.
METHODS: In vitro, Smad3 regulation was examined at both the level of transcription and translation in a human VF cell line in response to Smad3 siRNA ± transforming growth factor β (TGF-β). Collagen transcription was also examined. In vivo, Smad3 messenger RNA (mRNA) expression was quantified as a function of time following rabbit VF injury. Also, the effects of injected Smad3 siRNA were assessed at local and distal sites.
RESULTS: Smad3 siRNA knocked down Smad3 transcription and translation and limited TGF-β-mediated collagen mRNA expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1 day following VF injury and remained elevated through day 7. Smad3 siRNA injection into the uninjured vocal fold had no local or distant effect on Smad3 mRNA at multiple organ sites.
CONCLUSIONS: These data provide a foundation for further investigation regarding the development of novel RNA-based therapeutics for the VF, specifically locally delivered siRNA for challenging fibrotic conditions of the VF.
STUDY DESIGN: In vitro and in vivo.
METHODS: In vitro, Smad3 regulation was examined at both the level of transcription and translation in a human VF cell line in response to Smad3 siRNA ± transforming growth factor β (TGF-β). Collagen transcription was also examined. In vivo, Smad3 messenger RNA (mRNA) expression was quantified as a function of time following rabbit VF injury. Also, the effects of injected Smad3 siRNA were assessed at local and distal sites.
RESULTS: Smad3 siRNA knocked down Smad3 transcription and translation and limited TGF-β-mediated collagen mRNA expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1 day following VF injury and remained elevated through day 7. Smad3 siRNA injection into the uninjured vocal fold had no local or distant effect on Smad3 mRNA at multiple organ sites.
CONCLUSIONS: These data provide a foundation for further investigation regarding the development of novel RNA-based therapeutics for the VF, specifically locally delivered siRNA for challenging fibrotic conditions of the VF.
Предметные рубрики MeSH
AnimalsBlotting, WesternCells, CulturedElectrophoresis, Polyacrylamide GelFibrosisGene Expression RegulationGenetic TherapyHumansImmunohistochemistryLaryngeal DiseasesMaleRNA, MessengerRNA, Small InterferingRabbitsReverse Transcriptase Polymerase Chain ReactionSmad3 ProteinTransforming Growth Factor beta1Vocal Cords