Radiation fibrosis of the vocal fold

From man to mouse

Michael M. Johns, Vasantha Kolachala, Eric Berg, Susan Muller, Frances X. Creighton, Ryan C. Branski

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objectives/Hypothesis: To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis in order to ultimately develop both treatment and prevention paradigms. Design: Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods: 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis was identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray, as well as real-time transcriptional analyses, were performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results: Human irradiated vocal folds demonstrated increased collagen transcription, with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production, and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion: Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability occurring in patients following laryngeal irradiation. The irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis.

Original languageEnglish (US)
JournalLaryngoscope
Volume122
Issue numberSUPPL. 5
DOIs
StatePublished - Dec 2012

Fingerprint

Radiation Pneumonitis
Vocal Cords
Mucous Membrane
Laryngeal Muscles
Fibrosis
Collagen
Fibronectins
Immunohistochemistry
Genome
Radiation
Laryngectomy
Transforming Growth Factors
Laminin
Microarray Analysis
Glycosaminoglycans
Pliability
Real-Time Polymerase Chain Reaction
Oxidative Stress
Neck
Radiotherapy

Keywords

  • dysphonia
  • fibrosis
  • larynx
  • Level of Evidence: N/A.
  • radiation
  • Vocal fold
  • voice

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Johns, M. M., Kolachala, V., Berg, E., Muller, S., Creighton, F. X., & Branski, R. C. (2012). Radiation fibrosis of the vocal fold: From man to mouse. Laryngoscope, 122(SUPPL. 5). https://doi.org/10.1002/lary.23735

Radiation fibrosis of the vocal fold : From man to mouse. / Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

In: Laryngoscope, Vol. 122, No. SUPPL. 5, 12.2012.

Research output: Contribution to journalArticle

Johns, MM, Kolachala, V, Berg, E, Muller, S, Creighton, FX & Branski, RC 2012, 'Radiation fibrosis of the vocal fold: From man to mouse', Laryngoscope, vol. 122, no. SUPPL. 5. https://doi.org/10.1002/lary.23735
Johns MM, Kolachala V, Berg E, Muller S, Creighton FX, Branski RC. Radiation fibrosis of the vocal fold: From man to mouse. Laryngoscope. 2012 Dec;122(SUPPL. 5). https://doi.org/10.1002/lary.23735
Johns, Michael M. ; Kolachala, Vasantha ; Berg, Eric ; Muller, Susan ; Creighton, Frances X. ; Branski, Ryan C. / Radiation fibrosis of the vocal fold : From man to mouse. In: Laryngoscope. 2012 ; Vol. 122, No. SUPPL. 5.
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