Injection of Vocal Fold Lamina Propria-Derived Hydrogels Modulates Fibrosis in Injured Vocal Folds
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PROVIDER: PRJNA1255487 | ENA |
REPOSITORIES: ENA
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Project description:Vocal fold (VF) fibrosis, often caused by phonosurgery, radiation, or trauma, leads to irreversible voice dysfunction due to excessive ECM deposition and increased tissue stiffness. VF fibrosis, a significant cause of chronic dysphonia, lacks FDA-approved treatments, highlighting the critical need for novel antifibrotic therapeutic. TGF-β1 is a major driver in the pathological transformation of fibroblasts into contractile myofibroblasts in VF fibrosis via SMAD3, YAP1, and integrin signaling pathways. These pathways lead to increased ACTA2 expression, excessive collagen production, and progressive tissue stiffening. Leveraging the principle that local cells respond to tissue-specific signals, our ECM hydrogel derived from decellularized vocal fold lamina propria (VFLP-ECM) reduced ACTA2 expression in TGF-β1 stimulated vocal fold fibroblasts, showcasing antifibrotic potential. In this study, we evaluated the therapeutic potential of VFLP-ECM hydrogel in a rabbit VF injury model—treatment involved VFLP-ECM or bovine type I collagen injections into VFs 7 days after injury, with evaluations at 28 days post-injury. We compared two VFLP-ECM formulations: a manual process (VFLP (man)) and an accelerated automated method (VFLP (au)). VFLP (man) showed more modulated fibrosis-associated gene expressions when compared to VFLP (au) and collagen. Proteomic analysis revealed that VFLP (man) preserves a broader array of bioactive proteins, such as vitronectin, crucial in TGF-β1 signaling and ECM remodeling. The transcriptomic analysis uncovered a downregulation of key fibrotic markers and potential inhibition of regulators such as SMAD3, YAP1, and MRTFA, alongside the upregulation of SMAD7, an inhibitor of TGF-β signaling. Notably, treatment with VFLP (man) resulted in vocal folds with similar stiffness as uninjured controls, whereas tissues treated with collagen or VFLP (au) remained stiffer, indicating incomplete mechanical recovery. These data provide the first in vivo evidence that VFLP-ECM hydrogel—mainly when produced via manual decellularization—attenuates fibrosis by disrupting biochemical and biomechanical drivers of myofibroblast activation.
2025-07-29 | GSE295627 | GEO
Project description:We used microarrays to characterize transcriptome profiles of rat vocal fold tissue following surgical injury (vs. naive tissue); rat vocal fold fibroblasts harvested from scar tissue at the 60 d time point (vs. naive fibroblasts); rat vocal fold scar fibroblasts treated with siRNA against the collagen chaperone protein rat gp46 (vs. scramble siRNA). Adult Fischer 344 rat vocal fold tissue was harvested at 3, 14, and 60 days following surgical injury (control = age-matched naive tissue); rat vocal fold scar fibroblasts were obtained via explant culture of tissue obtained 60 days following surgical injury and harvested at 80% confluence during passage 1 (control = age-matched naive rat vocal fold fibroblasts); rat vocal fold scar fibroblasts were treated for 1 h with 50 nM liposome-delivered siRNA against rat gp46 when 80% confluent at passage 1, cultured for an additional 24 h in fresh media, then harvested (control = rat vocal fold scar fibroblasts treated with 50 nM liposome-delivered scramble siRNA).
2014-10-09 | E-GEOD-62204 | biostudies-arrayexpress
Project description:We used microarrays to characterize transcriptome profiles of rat vocal fold tissue following surgical injury (vs. naive tissue); rat vocal fold fibroblasts harvested from scar tissue at the 60 d time point (vs. naive fibroblasts); rat vocal fold scar fibroblasts treated with siRNA against the collagen chaperone protein rat gp46 (vs. scramble siRNA).
2014-10-09 | GSE62204 | GEO
Project description:The purpose of this study is to investigate if acute mucosal dehydration as a funcition of low relative humidty environment impacts the vocal folds at the mRNA level. Rabbits were used as animal model to enable a systematic and rigorous assessment of the pathobiology of vocal fold hydration since they can be manipulated in a physiologically realistic manner. We anticipate that the results of this study will help to elucidate the effects of altered mucosal hydration state in response to low ambient humidity on vocal fold epithelium, lamina propria and muscle tissue at the transcriptome level. Together with cellular, structural, and functional techniques that are part of this project, we expect to provide validated scientific recommendations on the adverse effects of mucosal dehydration and the therapeutic benefits of hydration.
2020-12-21 | GSE148588 | GEO
Project description:The purpose of this study is to investigate if acute systemic dehydration impacts the vocal folds at the mRNA level. Rabbits were used as animal model to enable a systematic and rigorous assessment of the pathobiology of vocal fold hydration since they can be manipulated in a physiologically realistic manner. We anticipate that the results of this study will help to elucidate the effects of altered hydration state in response to furosemide on vocal fold epithelium, lamina propria and muscle tissue at the transcriptome level. Together with cellular, structural, and functional techniques that are part of this project, we expect to provide validated scientific recommendations on the adverse effects of dehydration and the therapeutic benefits of hydration.
2020-07-09 | GSE132765 | GEO
Project description:Vocal folds (VFs) are exposed to external and internal stimuli that may cause damage leading to structural alterations and compromised function. Extracellular matrix (ECM)-based biomaterials have been explored as bioactive scaffolds to tissue repair. An injectable form of the VF-ECM scaffold would be an ideal biomaterial for minimally invasive delivery to injured VFs. The goal of this study was to develop a hydrogel form of VF lamina propria ECM (VFLP-ECM) and to characterize its properties and in vitro cellular response.
2021-05-25 | GSE125463 | GEO
Project description:Expression data from rat vocal fold at different periods after vocal fold injury
| PRJNA579528 | ENA
Project description:Expression data from rat vocal fold at different periods after vocal fold injury (miRNA)
| PRJNA614953 | ENA
Project description:Reinke’s edema is a cigarette associated, benign, mostly bilateral lesion of the vocal folds leading to dysphonia and dyspnea. Until today information about pathophysiology is only scarce, treatment is only surgical. To explore the pathophysiology of Reinke’s edema, we exposed near primary human vocal fold fibroblasts to cigarette smoke extract enriched medium or air bubbled control for 24 hrs. followed by a proteomic analysis. Proteomic analyses revealed an increase of proteins involved in oxidative stress response. We furthermore found that a significant number of essential extracellular matrix proteins was altered by culturing human VFF with CSE enriched medium: UDP-glucose 6-dehydrogenase, a protein involved in hyaluronan synthesis was upregulated, while the expression of several fibrillar collagen types was significantly reduced. The current findings corroborate previous studies but revealed new insights in possible disease mechanisms of Reinke’s edema too. We postulate that changes in the composition -reduction of collagen fibrils, increase of hyaluronan- of the vocal folds’ ECM may lead to the clinical findings.
2019-08-06 | PXD010640 | Pride
Project description:The objective of this study was to obtain a comprehensive proteome of euhydrated and systemically dehydrated rabbit vocal folds. We hypothesized that a mild-moderate systemic dehydration level would lead to changes in protein levels. New Zealand White rabbits were randomly assigned to euhydrated (control) or furosemide-dehydrated groups. Systemic dehydration was assessed by body weight loss and changes in blood markers. Vocal fold specimens were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry. Systemic dehydration induced 5.5 percent body weight loss (range: 4.5 to 6.5 percent) and significant changes in blood analytes compared to controls. More than 1500 proteins were identified across all vocal fold samples, associated with a variety of cellular components and ubiquitous cell functions such as protein synthesis and degradation, and mitochondrial translation and respiration. The comparison analysis identified 27 proteins differentially expressed in the systemically dehydrated vocal folds. These proteins are mainly involved with mitochondrial translation and metabolism, which are downregulated in response to systemic dehydration. We identified a large group of proteins representing the rabbit vocal fold tissue. The data provide novel insights on the response of vocal folds to a mild-moderate level of systemic dehydration that involves the downregulation of mitochondrial metabolism, suggesting a biologic mechanism to prevent oxidative damage associated with furosemide-induced dehydration.
2020-12-17 | MSV000086612 | MassIVE