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Effect of High Glucose on MUC5B expression in Human Airway Epithelial Cells
Sang Baik Ye1, Yoon Seok Choi1, Yo Han Choi1
1Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Gyeongsan, Korea.
Objectives:
Excessive production of mucus results in plugging of the airway tract, which can increase morbidity and mortality in affected patients. In patients with diabetes, inflammatory airway disease appears with more frequent relapse and longer duration of symptoms. However, the effects of high glucose (HG) on the secretion of mucin in inflammatory respiratory diseases are not clear. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of HG on MUC5B expression in human airway epithelial cells.
Methods:
The effect and signaling pathway of HG on MUC5B expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA.
Results:
HG increased MUC5B expression and epidermal growth factor receptor (EGFR) expression, and activated the phosphorylation of EGFR and p38 mitogen-activated protein kinase (MAPK). Pretreatment with EGFR inhibitor significantly attenuated the HG-induced phosphorylation of p38 MAPK, and pretreatments with p38 inhibitor or EGFR inhibitor significantly attenuated HG-induced MUC5B expression. In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked HG-induced MUC5B expression.
Conclusion:
These findings suggest that HG induces MUC5B expression via the sequential activations of the EGFR/p38 MAPK signaling pathway in human airway epithelial cells.
Insights
High glucose levels increase MUC5B expression in airway cells via the EGFR/p38 MAPK pathway. This finding is crucial for understanding mucus plugging in inflammatory respiratory diseases.
Area of Science:
- Respiratory Medicine
- Molecular Biology
- Cell Biology
Background:
- Excessive mucus production causes airway plugging, increasing patient morbidity and mortality.
- Diabetes is associated with more frequent and prolonged inflammatory airway disease relapses.
- The impact of high glucose on mucin secretion in respiratory diseases remains unclear.
Purpose of the Study:
- To investigate the effect of high glucose (HG) on MUC5B expression in human airway epithelial cells.
- To elucidate the signaling pathway involved in HG-induced MUC5B expression.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR were used to assess gene expression.
- Enzyme immunoassay and immunoblot analysis were employed to quantify protein levels.
- Specific inhibitors and small interfering RNA (siRNA) were utilized to investigate signaling pathways.
Main Results:
- High glucose significantly increased MUC5B and epidermal growth factor receptor (EGFR) expression.
- HG activated EGFR and p38 mitogen-activated protein kinase (MAPK) phosphorylation.
- EGFR and p38 MAPK inhibition or knockdown attenuated HG-induced MUC5B expression.
Conclusions:
- High glucose induces MUC5B expression in human airway epithelial cells.
- The EGFR/p38 MAPK signaling pathway is sequentially activated by HG to promote MUC5B expression.
- These findings offer insights into mucus hypersecretion mechanisms in diabetes-related respiratory conditions.
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