Abstract
Background
Insulin is involved in a glucose homeostatic regulation and a cellular metabolism via phosphorylation of phosphoinositide 3 kinase (PI3K) pathway and mitogen-activated protein kinase (MAPK) pathway. Hyperinsulinemia reduces insulin sensitivity and is an obvious potential factor affecting airway inflammation in chronic airway diseases. MUC5AC is a major secreted mucin, which plays a critical role in inflammatory response in the respiratory tract. However, the relationship between insulin and MUC5AC expression has not been studied.
Objective
This study investigated the effect and the brief signaling pathway of high concentration of insulin (HI) on MUC5AC expression in human airway epithelial cell.
Methods
In NCI-H292 cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of HI on MUC5AC expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).
Results
HI significantly increased MUC5AC expression and activated PI3K/AKT, extracellular signal-related kinase 1/2 (ERK1/2) and p38 MAPKs. The specific PI3K and AKT inhibitor as well as knockdown of AKT1 and AKT2 by the respective siRNAs significantly blocked HI-mediated expression of MUC5AC. Meanwhile, the specific ERK1/2 MAPK and p38 MAPK inhibitor as well as knockdown of ERK1, ERK2, and p38 MAPK by the respective siRNAs also attenuated HI-induced expression of MUC5AC.
Conclusion
The results of this study suggest that HI induces MUC5AC expression via PI3K/AKT and MAPK signaling pathways in human airway epithelial cells.
Keywords
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