Effects of transforming growth factor-beta1 on human vocal fold fibroblasts.
OBJECTIVE
We studied the effect of transforming growth factor (TGF)-beta 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-beta1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-beta signaling pathway were examined in this cell line.


RESULTS
TGF-beta stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutively expressed type I and II TGF-beta receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-beta isoforms. Exogenous TGF-beta1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-beta increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-beta decreased TGF-beta1 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-beta signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-beta 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.
Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Ryan C
RC
Branski
Silvia S
SS
Barbieri
Babette B
BB
Weksler
Benjamin
B
Saltman
Priya
P
Krishna
Dennis H
DH
Kraus
Nalini V
NV
Broadbelt
Jie
J
Chen
Dix P
DP
Poppas
Diane
D
Felsen
D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014827:Vocal Cords / Q000166:cytology* / Q000187:drug effects*
D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D003094:Collagen