Abstract
Cleavage of E-cadherin and the resultant weakness in the cell-cell links in the laryngeal epithelium lining is induced by exposure to acidic contents of the refluxate. Herein, we aimed to evaluate the role of matrix metalloproteinases (MMPs) in inducing E-cadherin level changes following acid exposure to the human pharyngeal mucosal cells. E-cadherin levels were inversely correlated with the duration of acid exposure. Treatment with actinonin, a broad MMP inhibitor, inhibited this change. Immunocytochemical staining and transepithelial permeability test revealed that the cell surface staining of E-cadherin decreased and transepithelial permeability increased after acid exposure, which was significantly inhibited by the MMP inhibitor. Among the various MMPs analyzed, the mRNA for MMP-7 in the cellular component was upregulated, and the secretion and enzymatic activity of MMP-7 in the culture media increased with the acid treatment. Consequently, MMP-7 plays a significant role in the degradation of E-cadherin after exposure to a relatively weak acidic condition that would be similar to the physiologic condition that occurs in Laryngopharyngeal reflux disease patients.
Highlights
Laryngopharyngeal reflux disease (LPRD) is an extraesophageal variant of gastroesophageal reflux disease (GERD) characterized by dysphonia, globus pharyngeus, hoarseness, recurrent throat clearing, and chronic cough
As cleavage of full-length E-cadherin into sE-cad is known to be enhanced by matrix metalloproteinases (MMPs) (Figure 1B), [21] the treatment of MMP inhibitor significantly reduced the cleavage of E-cadherin by acid exposure (Figure 1C, Supplementary Figure S2E)
The present study demonstrates that changes in E-cadherin in human pharyngeal epithelium by acid exposure may be mediated by MMP-7
Summary
Laryngopharyngeal reflux disease (LPRD) is an extraesophageal variant of gastroesophageal reflux disease (GERD) characterized by dysphonia, globus pharyngeus, hoarseness, recurrent throat clearing, and chronic cough. A diagnosis of LPRD can be established through a questionnaire for specific symptoms, a videolaryngoscopic evaluation of the larynx, or double-probe pH monitoring [4,5,6]. Ambulatory, 24-h double-probe (pharyngeal and esophageal) pH monitoring is both highly sensitive and specific for the diagnosis of LPRD [7,8]. It is not widely available in clinical practice due to its inconvenience and relatively high cost compared to more accessible videolaryngoscopic examination [9]
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