Regulation And Mechanism Of Aquaporin-5 To Mucin Hypersecretion

Partâ… Potential Effects of Aquaporin-5 in Allergic Inflammation and Airway Mucin Secretion in a Murine Model of AsthmaObjective Airway mucus hypersecretion is one of the characteristics of chronic airway diseases. The aquaporin (AQP)-5 has been proposed to contribute to the volume of liquid secreted from the upper airways. The purpose of the present study was to determine whether deletion of AQP5 impacts on mucin hypersecretion in the lower airways with dust mite (HDM)-induced chronic allergic pulmonary inflammation in AQP5+/+and AQP5-/-mice.Methods Bronchoalveolar lavage (BAL) levels of IL-2, IL-4, IL-10, interferon (IFN)-gamma and MUC5AC, and number of peribronchial and perivascular cells were measured.Results We found that HDM induced more airway inflammation, lung Th2 cell accumulation and mucin hypersecretion in the lungs of C57BL/6 mice rather than AQP5-/-mice. Lung tissue expression of MUC5AC and MUC5B protein and gene expression was significantly reduced in AQP5 knockout mice.Conclusions Our results implicate involvement of AQP5 in mucin secretion in a mouse model of chronic asthmatic inflammation.Partâ…¡Role of AQP5 in PMA induced MUC5AC mucin production in murine tracheal epithelia cells.Objective Primary culture of airway epithelia is a good model for studying differentiation process of epithelial cells. In this study we explored the role of AQP5 in PMA induced MUC5AC mucin production in murine tracheal epithelia cells and possible signaling pathways.Methods Murine tracheal epithelia cells grown at an air-liquid interface (ALI) were evaluated by scanning electron microscopy at 2 weeks of culture. After murine tracheal epithelia cells were stimulated with PMA for 24 hours, MUC5AC was determined by ELISA. Cells also were pretreated with PKC inhibitor Calphostinc after PMA stimulation. Western blotting was used to assess activation of the protein kinase C (PKC), p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2.Results Scanning electron micrograph demonstrated the cells were covered with numerous microvillus. Expression of cytokeratin 14 in mouse tracheal epithelial cells was positive. MUC5AC increased more in tracheal epithelia cells of AQP5 (-/-) mice than AQP5 (+/+) mice after PMA exposure. This effect was diminished in cells pretreated with Calphostinc. The phosphorylation of PKC/p38 but not (ERK) 1/2 induced by LPS was activated.Conclusions AQP5 affected MUC5AC production through Ca2+-PKC-p38 signaling pathways.Partâ…¢Aquaporin 5 Expression Inhibited by LPS via p38/JNK Signaling Pathway in SPC-A1 CellsObjective While goblet cell hyperplasia and mucus hypersecretion had been recognized as typical features of chronic obstructive pulmonary disease (COPD), recent studies suggested association of mucin secretion by submucosal glands cell with aquaporin 5 expression, or to be precise, decreased AQP5 expression correlated with increased staining of MUC5AC in submucosal glands of COPD patients. LPS is universally used to induce airway mucin secretion in vitro.Methods After SPC-A1 cells were stimulated with LPS, AQP5 and MUC5AC mRNA were determined by real-time PCR, AQP5 and MUC5AC protein were measured by western blotting and ELISA. SPC-A1 cells were pretreated with EGFR inhibitor AG1478, ERK inhibitor PD98059, p38 inhibitor ML3404, or JNK inhibitor SP600125 before LPS stimulation. AQP5 and MUC5AC mRNA were determined by RT-PCR.Results 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 p38/JNK signaling pathway, while MUC5AC was up-regulated through EGFR-p38/JNK pathway.Conclusions Therefore, p38 and JNK, their common signaling pathways, may become a promising target in our efforts of preserving AQP5 expression and preventing MUC5AC over expression to restore proper H2O/mucin ratio of airway mucus, which may be ultimately beneficial to COPD patients.