MUC5B mucin is a principal component of airway mucus and plays a key role in biodefense. We investigated the regulation of MUC5B production using the signals from extracellular matrix (ECM) components in NCI-H292 human lung epithelial cells. We found that MUC5B production in NCI-H292 cells cultured on fibronectin or laminin increased by 4–5-fold, with the increase occurring in a dose- and time-dependent manner. In contrast, MUC5B production was unchanged on type-IV collagen. Inhibition of integrin β1 induced upregulation of MUC5B and MUC5AC; however, inhibition of p38 MAPK did not show any remarkable change in overproduced MUC5B. Inhibition of extracellular signal-regulated kinase (ERK) pathway or the transcription factor NF-κB induced the recovery of overproduced MUC5B on fibronectin and laminin. These results suggest that MUC5B production can be regulated by ECM components and that MUC5B is upregulated by fibronectin and laminin via the integrin, ERK, and NF-κB dependent pathway.
In the human airway, the gel-forming mucin subtypes MUC5B and MUC5AC play important roles in biophylaxis. However, the regulation of MUC5B production is less clear than that of MUC5AC. Therefore, the regulation of MUC5B production by cell attachment and Akt was investigated in human lung epithelial NCI-H292 cells. We found that low cell attachment to culture plates induced the upregulated production of both MUC5B and MUC5AC. Cell attachment induces the activation of Akt, a serine/threonine kinase. Cell treatment with Akt inhibitor I decreased Akt phosphorylation and activation. However, MUC5B production was unaffected by Akt inhibition, whereas MUC5AC production was upregulated. MUC5B production was also unaffected by Akt inhibition in cells cultured on type IV collagen or fibronectin. These results suggest that the production of both MUC5B and MUC5AC is regulated by cell attachment. However, the regulation of MUC5B is unaffected by Akt inhibition, in contrast to that of MUC5AC.
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