MUC5B mucin production is upregulated by fibronectin and laminin in human lung epithelial cells via the integrin and ERK dependent pathway

Abstract

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.

MUC5B mucin plays a key role in biodefense. Our results suggest that a signal from fibronectin and laminin induce upregulation of MUC5B, mediated by integrin pathway and ERK pathway.

Key words:

• MUC5B
• MUC5AC
• mucin
• extracellular matrix
• integrin

Acknowledgments

The authors thank Dr Hajime Muraguchi for his helpful advices.

Notes

Abbreviations: ECM, extracellular matrix; COPD, chronic obstructive pulmonary disease; ERK, extracellular-signal-regulated kinases.