Insulin is involved in glucose homeostatic regulation and cellular metabolism via phosphorylation of phosphoinositide three kinases (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 the respiratory tract’s inflammatory response. However, the relationship between insulin and MUC5AC expression has not been studied.
This study investigated the effect and the short signaling pathway of high insulin concentration (HI) on MUC5AC expression in human airway epithelial cell.
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 RT-PCR, real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and siRNA.
HI significantly increased MUC5AC expression and activated PI3K/AKT, ERK1/2, and p38 MAPKs. The specific PI3K and AKT inhibitor and 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.
The study concluded that HI induces MUC5AC expression via PI3K/AKT and MAPK signaling pathways in human airway epithelial cells.