Regulator of G-protein signaling 2 inhibits acid-induced mucin5AC hypersecretion in human airway epithelial cells.
Mucus hypersecretion is a common pathological feature of inflammatory airway diseases. Previous studies have shown that acidic microenvironment of inflamed airways may provoke the pathophysiology of inflammatory airway diseases. However, the acidic-sensing and negative regulatory mechanisms that mediate mucus hypersecretion in inflamed airway remain elusive. Thus, we sought to explore the role of ovarian cancer G-protein-coupled receptor 1 (OGR1) in acid-induced mucin5AC (MUC5AC) hypersecretion in human airway epithelium and the inhibitory effect of regulator of G-protein signaling 2 (RGS2) in this process. We found that airway acidification increased [Ca(2+)](i), which was required for MUC5AC secretion. Knocking-down OGR1 and G(q) with siRNAs and pretreating cells with phospholipase C inhibitor effectively attenuated acid-induced cellular responses. Moreover, the overexpression of wild-type RGS2 attenuated acid-induced cellular responses. In contrast, reducing RGS2 with siRNA enhanced the increases in acid-induced cellular responses. These data suggest that airway acidification can induce MUC5AC hypersecretion through an OGR1-mediated mechanism and RGS2 can inhibit acid-induced MUC5AC hypersecretion at OGR1 receptor level.
Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing 400010, China.
Chunyi
C
Liu
Qi
Q
Li
Xiangdong
X
Zhou
Victor P
VP
Kolosov
Juliy M
JM
Perelman
D000143:Acids / Q000494:pharmacology*; D000704:Analysis of Variance; D001980:Bronchi / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047468:Immunoprecipitation; D055271:Mucin 5AC / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D020710:RGS Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014316:Tritium / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D000143:Acids; D002614:Chelating Agents; C486281:GPR68 protein, human; D055271:Mucin 5AC; D020710:RGS Proteins; C087182:RGS2 protein, human; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D014316:Tritium; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D002118:Calcium