| First Author | Song KS | Year | 2009 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 296 |
| Issue | 4 | Pages | L684-92 |
| PubMed ID | 19201815 | Mgi Jnum | J:149688 |
| Mgi Id | MGI:3848866 | Doi | 10.1152/ajplung.90396.2008 |
| Citation | Song KS, et al. (2009) Suppression of prostaglandin E2-induced MUC5AC overproduction by RGS4 in the airway. Am J Physiol Lung Cell Mol Physiol 296(4):L684-92 |
| abstractText | The mechanism by which E-prostanoid (EP) receptor is critically involved in PGE(2)-induced mucin 5AC (MUC5AC) gene expression in the airway has been unclear. Furthermore, there have been little reports regarding the negative regulatory mechanism and/or proteins that affect PGE(2)-induced MUC5AC overproduction. In the present study, we found that PGE(2) induced MUC5AC gene expression in a dose-dependent manner (EC(50): 73.31 +/- 3.13 nM) and that the EP(2/4)-specific agonist, misoprostol, increased MUC5AC mRNA level, whereas the EP(1/3)-specific agonist, sulprostone, had no effect. Interestingly, the cAMP concentration (685.1 +/- 14.9 pM) of the EC(50) value of EP(4)-mediated cAMP production was much higher than that of EP(2) (462.33 +/- 23.79 pM), suggesting that EP(4) has higher sensitivity to PGE(2) compared with EP(2). Moreover, PGE(2)-induced Muc5ac overproduction was much increased in regulator of G protein signaling (Rgs) 4 knockout (KO) mice compared with wild-type mice at both transcriptional and translational levels, and it was dramatically suppressed in Rgs4 KO mice that had been infected with lentivirus expressing RGS4 (lenti::RGS4) compared with lentivirus expressing enhanced green fluorescent protein (lenti::eGFP). Finally, we demonstrate that PGE(2) can induce MUC5AC overproduction via the EP(4) receptor and that RGS4 may have suppressive effects in controlling MUC5AC overexpression in the airway. These findings may provide a molecular paradigm for the development of novel drugs for respiratory diseases. |
