Characterisation of adherens and tight junctional molecules in normal animal larynx; determining a suitable model for studying molecular abnormalities in human laryngopharyngeal reflux

Gill, Gulnaz A.; Buda, Andrea; Moorghen, M; Dettmar, Peter W.; Pignatelli, Massimo

doi:10.1136/jcp.2004.016972

Cited by 39 publications

(39 citation statements)

References 35 publications

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“…10 Adherens junctions and desmosomes were also observed consistent with their presence in humans. [10][11][12] However, despite the presence of intercellular …”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in addition to demonstrating an epithelial phenotype, candidate tissue constructs must also demonstrate the presence of important components of the epithelial barrier, including intercellular junctions. The native vocal fold epithelium contains intercellular junctions, including tight junctions, 10,11 gap junctions, 12 adherens junctions, 11 and desmosomes. 10 While Long and colleagues 9 reported the presence of e-cadherin, a marker of adherens junctions, in their model, further evidence of intercellular junctions was not provided.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human Embryonic Stem Cell-Derived Epithelial Cells in a Novel In Vitro Model of Vocal Mucosa

Leydon

Selekman

Palecek

et al. 2013

Tissue Engineering Part A

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A satisfactory in vitro model of vocal fold mucosa does not exist, thus precluding a systematic, controlled study of vocal fold biology and biomechanics. We sought to create a valid, reproducible three-dimensional (3D) in vitro model of human origin of vocal fold mucosa of human origin. We hypothesized that coculture of human embryonic stem cell (hESC)-derived simple epithelial cells with primary vocal fold fibroblasts under appropriate conditions would elicit morphogenesis of progenitor cells into vocal fold epithelial-like cells and creation of a basement membrane. Using an in vitro prospective study design, hESCs were differentiated into cells that coexpressed the simple epithelial cell marker, keratin 18 (K18), and the transcription factor, p63. These simple epithelial cells were cocultured with primary vocal fold fibroblasts seeded in a collagen gel scaffold. The cells were cultured for 3 weeks in a keratinocyte medium at an air-liquid interface. After that time, the engineered mucosa demonstrated a stratified, squamous epithelium and a continuous basement membrane recapitulating the key morphologic and phenotypic characteristics of native vocal fold mucosa. hESC-derived epithelial cells exhibited positive staining for vocal fold stratified, squamous epithelial markers, keratin 13 (K13) and 14 (K14), as well as tight junctions, adherens junctions, gap junctions, and desmosomes. Despite the presence of components critical for epithelial structural integrity, the epithelium demonstrated greater permeability than native tissue indicating compromised functional integrity. While further work is warranted to improve functional barrier integrity, this study demonstrates that hESC-derived epithelial progenitor cells can be engineered to create a replicable 3D in vitro model of vocal fold mucosa featuring a multilayered, terminally differentiated epithelium.

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“…10 Adherens junctions and desmosomes were also observed consistent with their presence in humans. [10][11][12] However, despite the presence of intercellular …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Embryonic Stem Cell-Derived Epithelial Cells in a Novel In Vitro Model of Vocal Mucosa

Leydon

Selekman

Palecek

et al. 2013

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…The cytoplasmic tails of cadherins bind members of the armadillo protein family, such as β-catenin. Cadherins communicate with the actin cytoskeleton through contacts with β-catenin (7).…”

Section: Introductionmentioning

confidence: 99%

Restoration of desmosomal junction protein expression and inhibition of H3K9-specific histone demethylase activity by cytostatic proline-rich polypeptide-1 leads to suppression of tumorigenic potential in human chondrosarcoma cells

Galoian

Qureshi

Wideroff

et al. 2014

Molecular and Clinical Oncology

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Abstract. Disruption of cell-cell junctions and the concomitant loss of polarity, downregulation of tumor-suppressive adherens junctions and desmosomes represent hallmark phenotypes for several different cancer cells. Moreover, a variety of evidence supports the argument that these two common phenotypes of cancer cells directly contribute to tumorigenesis. In this study, we aimed to determine the status of intercellular junction proteins expression in JJ012 human malignant chondrosarcoma cells and investigate the effect of the antitumorigenic cytokine, proline-rich polypeptide-1 (PRP-1) on their expression. The cell junction pathway array data indicated downregulation of desmosomal proteins, such as desmoglein (1,428-fold), desmoplakin (620-fold) and plakoglobin (442-fold). The tight junction proteins claudin 11 and E-cadherin were also downregulated (399-and 52-fold, respectively). Among the upregulated proteins were the characteristic for tumors gap junction β-5 protein (connexin 31.1) and the pro-inflammatory pathway protein intercellular adhesion molecule (upregulated 129-and 43-fold, respectively). We demonstrated that PRP-1 restored the expression of the abovementioned downregulated in chondrosarcoma desmosomal proteins. PRP-1 inhibited H3K9-specific histone demethylase activity in chondrosarcoma cells in a dose-dependent manner (0.5 µg/ml PRP, 63%; 1 µg/ml PRP, 74%; and 10 µg/ml PRP, 91% inhibition). Members of the H3K9 family were shown to transcriptionally repress tumor suppressor genes and contribute to cancer progression. Our experimental data indicated that PRP-1 restores tumor suppressor desmosomal protein expression in JJ012 human chondrosarcoma cells and inhibits H3K9 demethylase activity, contributing to the suppression of tumorigenic potential in chondrosarcoma cells.

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“…The authors indicated that the porcine larynx was a superior model for research of epithelial damage occurring during LPR. 21 In the present study, Bama minipigs were used. The miniature pig has been widely accepted as the experimental animal.…”

Section: Discussionmentioning

confidence: 99%

“…The Bama minipigs were 4-6 months old, the mean weight was 10 kg, and the mean length was 71 cm. Minipigs were maintained in a pathogen-free environment with a 12:12-hour light-dark cycle, temperature (20)(21)(22) o C) and humidity (50-60%) for 1 week prior to experiment in order to adapt to environment. Ten Bama minipigs were randomly divided into control group and stent group.…”

Section: Animalsmentioning

confidence: 99%

A Bama Minipig Model of Laryngopharyngeal Reflux and the Change of Laryngopharyngeal Mucosal Ultrastructure

Feng

Zhang²,

Chun-yan

et al. 2015

J Neurogastroenterol Motil

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Background/Aims To establish an animal model of laryngopharyngeal reflux (LPR) and study the effect of LPR on the laryngopharyngeal mucosal ultrastructure. Methods Ten Bama minipigs were randomly divided into control group and stent group. Every pig underwent endoscope, and baseline pH was monitored for 4 hours at laryngopharynx and distal esophagus, then specimens from laryngopharyngeal mucosa were biopsied. For the control group, these procedures were repeated on the 14th day. In the stent group, a custom-designed esophageal stent suit was implanted into esophagus, laryngopharyngeal and distal esophageal pH monitoring lasted for 2 hours, then stent suit was removed 3 days later. At last, the same procedures were done as the control group on the 14th day. Specimens were observed under transmission electron microscope to measure the intercellular space and desmosome number. Results In the control group, there was no laryngopharyngeal reflux on the first day and 14th day. Before the stent was implanted, there was also no laryngopharyngeal reflux in the stent group. In both 2 hours and 14 days after stent implantation, the num -ber of reflux, reflux time, and percentage time of pH < 4.0 were significantly increased ( P < 0.05) in the stent group. There was no difference in intercellular space and desmosomes in the control group between baseline and 14th day. In the stent group, intercellular space of laryngopharyngeal mucosa was significantly increased (0.37 μm vs 0.96 μm, P = 0.008), and the number of desmosomes was significantly decreased (20.25 vs 9.5, P = 0.003). Conclusions A Bama minipig model of LPR was established by implanting a custom-designed stent suit. LPR might destroy the laryngophar yngeal mucosal barrier.

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Characterisation of adherens and tight junctional molecules in normal animal larynx; determining a suitable model for studying molecular abnormalities in human laryngopharyngeal reflux

Cited by 39 publications

References 35 publications

Human Embryonic Stem Cell-Derived Epithelial Cells in a Novel In Vitro Model of Vocal Mucosa

Human Embryonic Stem Cell-Derived Epithelial Cells in a Novel In Vitro Model of Vocal Mucosa

Restoration of desmosomal junction protein expression and inhibition of H3K9-specific histone demethylase activity by cytostatic proline-rich polypeptide-1 leads to suppression of tumorigenic potential in human chondrosarcoma cells

A Bama Minipig Model of Laryngopharyngeal Reflux and the Change of Laryngopharyngeal Mucosal Ultrastructure

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