Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Hortobagyi, D.
Exploring the Pathophysiology of Vocal Fold Inflammation: The Molecular Impact of Vibration
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp. 117
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Gugatschka Markus
- Obermayer-Pietsch Barbara
- Wadsack Christian
- Altmetrics:
- Abstract:
- Introduction The biological basis of voice rest following a traumatic event, such as vocal overuse, or pho- nosurgery, remains unanswered as purely explorative invasive interventions of the vocal folds in humans cannot be carried out due to ethical reasons. Aim of our study was to study the cellular behavior of human vocal fold fibroblasts (hVFF), being the main cellular component of the lamina propria, under dynamic (‘vocal load’) and static (‘voice rest’) conditions following an inflammatory stimulus. Methods hVFF were seeded onto flexible membraned six-well-plates and exposed to a predefined vi- brational stress pattern by using a phonomimetic bioreactor. Additionally, inflammatory and profibrotic stimuli were induced by adding interleukin (IL)1β and transforming growth factor (TGF)β1. Mechanical stimulation was applied four hours daily, over a period of 72 hours. Out- come measurements comprised assessment of extracellular matrix (ECM)-related compo- nents, angiogenic factors, and inflammatory and fibrogenic markers on gene expression and protein levels. Results Quantitative polymerase chain reaction (qPCR) showed a significant increase in the expres- sion of different key proteins during an inflammatory reaction, reflecting that these stimuli were effective. Under inflammatory conditions, the inflammatory cytokine IL11, as well as the myo- fibroblast marker alpha smooth muscle actin (α-SMA) were significantly reduced when addi- tional vibration was applied. The desirable anti-fibrotic extracellular matrix component hyalu- ronic acid was increased following cytokine treatment, was however not diminished following vibration. Discussion Clinical recommendations and treatment strategies need to be based on biological mecha- nisms, however remaining an unmet goal, as human VF cannot be repeatedly biopsied. Our experiments showed the effect of vibrational stress on hVFF in an inflammatory state. Elevated levels of certain pro-inflammatory/pro-fibrotic factors could be mitigated by additional vibra- tional excitation in an in vitro setting. These findings corroborate clinical studies, recommend- ing early voice activation following an acute event.