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- Title
The role of Smad3 in the fibrotic phenotype in human vocal fold fibroblasts.
- Authors
Branski, Ryan C.; Bing, Renjie; Kraja, Iv; Amin, Milan R.
- Abstract
<bold>Objectives/hypothesis: </bold>To investigate the role of Smad3 as a regulator of transforming growth factor (TGF)-β1-mediated cell activities associated with fibrosis in normal human vocal fold fibroblasts. We also sought to confirm the temporal stability of Smad3 knockdown via small inhibitor ribonucleic acid (siRNA). Vocal fold fibroblasts were employed to determine the effects of Smad3 knockdown on TGF-β1-mediated migration and contraction, as well as regulation of connective tissue growth factor (CTGF). We hypothesized that Smad3 is an ideal candidate for therapeutic manipulation in vivo based on its role in fibrosis.<bold>Study Design: </bold>In vitro.<bold>Methods: </bold>Knockdown of Smad3 via siRNA was performed in our normal human vocal fold cell line. Three-dimensional collagen gel contraction and scratch assays were employed to determine the role of Smad3 on TGF-β1-mediated contraction and migration, respectively. The role Smad3 in the induction of CTGF was characterized via sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of Smad3 signaling on Smad7 messenger (m)RNA and protein were also quantified.<bold>Results: </bold>Smad3 knockdown was temporally-stable up to 72 hours (P < 0.001), diminished TGF-β1-mediated collagen gel contraction and migration, and blunted induction of CTGF, but it had no effect on TGF-β1-mediated Smad7 mRNA or protein induction.<bold>Conclusion: </bold>Transforming growth factor-β1 stimulated profibrotic cell activities in our cell line and these actions were largely reduced with Smad3 knockdown. These data provide continued support for therapeutic targeting of Smad3 for vocal fold fibrosis because it appears to regulate the fibrotic phenotype.<bold>Level Of Evidence: </bold>N/A. Laryngoscope, 126:1151-1156, 2016.
- Subjects
SMAD proteins; FIBROSIS; VOCAL cord diseases; PHENOTYPES; TRANSFORMING growth factors-beta; FIBROBLASTS; CONNECTIVE tissue growth factor; COLLAGEN diseases; GENETICS; THERAPEUTICS; CARRIER proteins; CELL lines; GROWTH factors; RESEARCH funding; RNA; VOCAL cords; CHEMICAL inhibitors
- Publication
Laryngoscope, 2016, Vol 126, Issue 5, p1151
- ISSN
0023-852X
- Publication type
journal article
- DOI
10.1002/lary.25673