Effects of transforming growth factor-β1 on human vocal fold fibroblasts Journal Article
| Authors: | Branski, R. C.; Barbieri, S. S.; Weksler, B. B.; Saltman, B.; Krishna, P.; Kraus, D. H.; Broadbelt, N. V.; Chen, J.; Poppas, D. P.; Felsen, D. |
| Article Title: | Effects of transforming growth factor-β1 on human vocal fold fibroblasts |
| Abstract: | Objectives: We studied the effect of transforming growth factor (TGF)-β on immortalized human vocal fold fibroblasts. Methods: Normal human vocal fold fibroblasts were subjected to sequential lentiviral transduction with genes for human telomerase (hTERT) and SV40 large T antigen in order to produce an "immortalized" cell line of normal phenotype. After confirmation of vocal fold fibroblast transfection, these cells, referred to as HVOX, were treated with various concentrations of exogenous TGF-β1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-β signaling pathway were examined in this cell line. Results: TGF-β stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutively expressed type I and II TGF-β receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-β isoforms. Exogenous TGF-β1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-β increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-β decreased TGF-β1 gene expression. Conclusions: Insight into the underlying pathophysiology of vocal fold fibrosis is likely to yield improved therapeutic strategies to mitigate vocal fold scarring. Our data suggest that TGF-β signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-β may be a reasonable target for therapies to prevent and/or treat vocal fold fibrosis, given its putative role in both acute and chronic vocal fold injury, as well as its effects on vocal fold fibroblasts. © 2009 Annals Publishing Company. All rights reserved. |
| Keywords: | signal transduction; adult; controlled study; human cell; case report; vocal cord; pathophysiology; cell proliferation; phenotype; gene expression; smad protein; smad2 protein; smad3 protein; smad7 protein; transforming growth factor beta; cell line; dose-response relationship, drug; genetic transduction; fibrosis; genetic transfection; messenger rna; signal peptide; collagen; lentivirus vector; transforming growth factor; vocal fold; voice; telomerase reverse transcriptase; transforming growth factor beta receptor; transforming growth factor beta1; virus large t antigen; autocrine effect; cell migration; fibroblast; paracrine signaling; protein secretion; scar formation; simian virus 40; vocal fold fibrosis; cell culture techniques; fibroblasts; receptors, transforming growth factor beta; smad proteins; vocal cords |
| Journal Title: | Annals of Otology Rhinology and Laryngology |
| Volume: | 118 |
| Issue: | 3 |
| ISSN: | 0003-4894 |
| Publisher: | Annals Publ Co |
| Date Published: | 2009-03-01 |
| Start Page: | 218 |
| End Page: | 226 |
| Language: | English |
| PUBMED: | 19374154 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: AORHA" - "Source: Scopus" |
Citation Impact
Related MSK Work