Abstract: Objectlve To explore the signal pathway of calcium-sensing receptor (CaSR) in hypoxia-induced airway mucous hypersecretion. Methods Cultured human airway epithelial cells 16HBE by hypoxia incubator (37 oC,94%N2-1%O2-5%CO2) and divided into 6 groups:control group,hypoxia group,CaSR specific activator CaCl2 group treated with hypoxia,negative-siRNA control group treated with hypoxia,CaSR-siRNA group treated with hypoxia,extracellular signal regulated kinase(ERK) specific inhibitor U0126 group treated with hypoxia.The levels of MUC5AC mRNA were detected by RT-PCR.The protein levels of CaSR,ERK and phosphorylated ERK(p-ERK) were detected by Western blot.The levels of MUC5AC secretion were measured by ELISA.Cell survival rate was measured by MTT assay. Results CaSR protein was expressed in 16HBE and transfection with CaSR-siRNA significantly inhibited the expression of CaSR.In hypoxia group,the levels of p-ERK,MUC5AC mRNA and MUC5AC protein were increased (0.63±0.11,0.51±0.03,0.56±0.07) versus the control group (0.27±0.04,0.18±0.04,0.25±0.06) (P<0.05).CaCl2(a CaSR agonist) amplified the effect of hypoxia(P<0.05). Transfection with CaSR-siRNA or pretreatment with ERK inhibitor decreased the levels of p-ERK,MUC5AC mRNA and MUC5AC protein induced by hypoxia(P<0.05).Conclusion CaSR mediates hypoxia-induced airway mucous hypersecretion through MEK/ERK1/2 signaling pathway.

Key words: calcium-sensing receptor, hypoxia, mucin, ERK