Dataset Information

Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells.

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.

SUBMITTER: Im NR

PROVIDER: S-EPMC6862869 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells.

Im Nu-Ri NR Lee Doh Young DY Kim Byoungjae B Kim Jian J Jung Kwang-Yoon KY Kim Tae Hoon TH Baek Seung-Kuk SK

International journal of molecular sciences 20191024 21

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. Immuno ...[more]

PMID: 31652949

Similar Datasets

Project description:Laryngopharyngeal reflux disease (LPRD) is caused by pharyngeal mucosal damage due to the reflux of gastric contents, including acid, pepsin, and bile juice. Our previous study has demonstrated that LPRD is associated with the cleavage of E-cadherin, which is facilitated by the acid-activated matrix metalloproteinase-7 (MMP-7); however, the mechanism by which the acid activates MMP-7 remains unclear. The purpose of this study was to investigate the mechanism by which MMP-7 is activated in the pharyngeal epithelial cells that are exposed to acid. The levels of reactive oxygen species (ROS) were measured in the epithelial cells exposed to acid. To investigate the signaling mechanism of ROS in the expression of MMP-7, the mechanism of action of the mitogen-activated protein kinase was examined. The expression of various signaling factors was determined, according to the presence or absence of each inhibitor in the acid-exposed pharyngeal epithelial cells. To identify changes in the cleavage of E-cadherin, the integrity of the mucosal membrane was assessed using a transepithelial permeability test. We found that acid exposure increased the levels of ROS, phosphorylated-extracellular signal-regulated kinase (p-ERK) 1/2, and phosphorylated-c-Jun (p-c-Jun) in pharyngeal epithelial cells. The ROS inhibitor reduced the expression of p-ERK and MMP-7, while the ERK inhibitor reduced the expression of p-c-Jun and MMP-7. Moreover, the c-Jun inhibitor reduced the expression of MMP-7 and blocked the degradation of E-cadherin. In addition, decrease in the levels of immunostained E-cadherin and increase in transepithelial permeability after acid exposure were collectively alleviated by the inhibitors of ROS, ERK, and c-Jun. The degradation of E-cadherin that occurs after human mucosal cells are exposed to acid appears to be caused by an increase in the expression of MMP-7 via the ROS/ERK/c-Jun pathway, which is thought to be an important mechanism associated with the development of LPRD. KEY MESSAGES: • ROS is triggered when reflux occurs. • ROS regulates the transcription factor c-Jun via the ERK pathway. • The increase in MMP-7 that induces LPRD is induced via the ROS/ERK/c-Jun pathway. • This study revealed for the first time the expression mechanism of MMP-7, which is one of the causes of LPRD.

Project description:OBJECTIVES:This study was conducted to investigate the current practices of Asian otolaryngologists for laryngopharyngeal reflux (LPR). METHODS:An online survey about LPR was sent to 2,000 members of Asian otolaryngological societies, and a subgroup analysis was performed between Western and Eastern Asian otolaryngologists. The survey was conducted by the Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies. RESULTS:Among approximately 1,600 Asian otolaryngologists, 146 completed the survey (62 from Western Asian countries, 84 from Eastern Asian countries). A substantial majority (73.3%) of the otolaryngologists considered LPR and gastroesophageal reflux disease to be different diseases. The symptoms thought to be closely related to LPR were coughing after lying down, throat clearing, and globus sensation. The findings thought to be closely related to LPR were posterior commissure granulations and hypertrophy, arytenoids, and laryngeal erythema. The respondents indicated that they mostly diagnosed LPR (70%) after an empirical therapeutic trial of proton pump inhibitors (PPIs). Although multichannel intraluminal impedance-pH (MII-pH) monitoring is a useful tool for diagnosing nonacid or mixed LPR, 78% of Asian otolaryngologists never or very rarely used MII-pH. Eastern Asian otolaryngologists more frequently used once-daily PPIs (64.3% vs. 45.2%, P=0.021), whereas Western Asian otolaryngologists preferred to use twice-daily PPIs (58.1% vs. 39.3%, P=0.025). The poor dietary habits of patients were considered to be the main reason for therapeutic failure by Asian otolaryngologists (53.8%). Only 48.6% of Asian otolaryngologists considered themselves to be adequately knowledgeable and skilled regarding LPR. CONCLUSION:Significant differences exist between Western and Eastern Asian otolaryngologists in the diagnosis and treatment of LPR. Future consensus statements are needed to establish diagnostic criteria and therapeutic regimens.

Dataset Information

Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells.

Publications

Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets