Aquaporin 5 expression inhibited by LPS via p38/JNK signaling pathways in SPC-A1 cells.

Proper H(2)O to mucin ratio of airway mucus is important for mucociliary clearance. Recent studies suggest that decreased aquaporin 5 (AQP5) is correlated with increased staining of MUC5AC in submucosal glands of COPD patients. Lipopolysaccharide (LPS) is one of the major insults in airway mucin secretion in COPD. In this study, changes in both AQP5 and MUC5AC expression levels in SPC-A1, a human airway submucosal gland cell line, were quantified after exposure of the cells to LPS. AQP5 transcription and protein expression were decreased while MUC5AC expression was increased by LPS exposure in SPC-A1 cells. Further studies revealed that AQP5 expression was down-regulated via the p38/JNK signaling pathway, while MUC5AC was up-regulated through the EGFR-p38/JNK pathway. Therefore, p38 and JNK may become promising targets to preserve AQP5 expression and prevent MUC5AC over-expression to restore proper H(2)O to mucin ratio of the airway mucus, which may be beneficial to the clinical management of COPD patients.