Tamoxifen Alters TGF-ß1/Smad Signaling in Vocal Fold Injury.
Laryngoscope
; 133(9): 2248-2254, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-36250536
ABSTRACT
OBJECTIVES:
Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-ß1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.METHODS:
In vitro, vocal fold fibroblasts were treated with TAM (10-8 or 10-9 M) ± TGF-ß1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.RESULTS:
TAM (10-8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10-8 or 10-9 M) + TGF-ß1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-ß1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.CONCLUSIONS:
TAM has antifibrotic potential via the regulation of TGF-ß1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis. LEVEL OF EVIDENCE NA Laryngoscope, 1332248-2254, 2023.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tamoxifen
/
Vocal Cords
/
Selective Estrogen Receptor Modulators
/
Smad Proteins
/
Transforming Growth Factor beta1
/
Vocal Cord Dysfunction
/
Antifibrotic Agents
Type of study:
Clinical_trials
Limits:
Animals
Language:
En
Journal:
Laryngoscope
Year:
2023
Document type:
Article