Objective    To study the effect of chronic mechanical stress on mucin (MUC)5AC expression in airway epithelial cells of rats and its possible signaling pathway.     Methods    Airway epithelial cells from rats were cultured on transwell membrane at an air-liquid interface

stimulated by chronic mechanical stress from air pressure and pre-treated with EGFR kinase inhibitor AG1478 and specific inhibitor of the ERK pathway PD-98059

respectively. The cells were divided into negative control group

stress treatment group

AG1478 pre-treatment group

and PD98059 pre-treatment group. Chronic mechanical stress was induced by 10

20 and 30 cmH

2

O

respectively in stress treatment group. MUC5AC protein was detected by enzyme-linked immunosorbent assay. MUC5AC mRNA level was analyzed by RT-PCR. Protein levels of p-JNK

p-ERK and p-P38 were measured by Western blotting.     Results    The protein level of MUC5AC

mRNA and p-ERK was significantly higher in stress group than in control group (P0.05). However

no significant difference was found in protein level of p-JNK and p-P38 between stress and control groups (P0.05). The expression level of MUC5AC protein and mRNA was significantly higher in 30 cmH

2

O stress group than in control group (0.65±0.09 and 0.62±0.07  vs 0.28±0.04 and 0.20±0.05

P0.01). The expression level of p-ERK was also significantly higher in 30 cmH

2

O stress group (0.68±0.05) than in control group (0.27±0.07

P0.01). After pre-treatment with AG1478 and PD98059

the protein and mRNA expression levels of MUC5AC

  and protein expression level of p-ERK was 0.39±0.08

0.40±0.06

0.25±0.04 in AG1478 pre-treatment+30 cmH

2

O group

and 0.36±0.09

0.38±0.13

0.26±0.11 in PD98059 pre-treatment+30 cmH

2

O group

which was significantly lower than in 30 cmH

2

O stress group (P0.05).     Conclusion    Chronic mechanical stress can significantly up-regulate the exp

ression of MUC5AC protein and mRNA by compressing the lateral intercellular space. EGFR and ERK signal pathways play a key role in the process.