Integrin ß1 subunit regulates cellular and secreted MUC5AC and MUC5B production in NCI-H292 human lung epithelial cells.

ABSTRACT

The surface of the human respiratory tract is covered with a mucus layer containing mucin 5AC (MUC5AC) and mucin 5B (MUC5B) as the main components. This layer contributes to biological defense by eliminating irritants, but excessive MUC5AC secretion by the airway epithelial cells exacerbates asthma. Therefore, regulating mucin production is important for asthma treatment. In this study, the effects of integrin ß1 subunit on MUC5AC and MUC5B production were examined in NCI-H292 human lung cancer epithelial cells. When integrin ß1 was overexpressed, cellular and secreted MUC5AC levels were decreased, whereas cellular MUC5B production was increased. Conversely, integrin ß1 depletion using siRNA increased cellular and secreted MUC5AC production, but decreased cellular MUC5B production. Further, the activity of extracellular signal-regulated kinase (ERK), which promotes MUC5AC production, was decreased by integrin ß1 overexpression and increased by its depletion. These results suggest that integrin ß1 suppresses MUC5AC production and promotes MUC5B production by downregulating ERK.