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Regulator of G-protein signaling 4 suppresses LPS-induced MUC5AC overproduction in the airway.

Authors
Song, KS; Kim, HJ; Kim, K; Lee, JG; Yoon, JH
Citation
American journal of respiratory cell and molecular biology, 41(1):40-49, 2009
Journal Title
American journal of respiratory cell and molecular biology
ISSN
1044-15491535-4989
Abstract
Mucus overproduction and airway obstruction are common features in airway mucosal inflammation. The mechanism by which LPS induces MUC5AC overexpression, however, has not been fully explored. The aims of this study were twofold: first, to examine the ATP-dependent mechanism by which LPS induces MUC5AC gene expression, and second, to identify specific molecules that could suppress LPS-induced MUC5AC expression at a G-protein-coupled receptor level. Here, we suggest that LPS from Pseudomonas aeruginosa induces MUC5AC overproduction by both an ATP-dependent pathway and an ATP-independent pathway. In addition, we showed that Regulator of G-protein signaling (RGS) 4 plays as a suppressor for ATP-induced MUC5AC expression by interacting with G alpha q in a GTP-dependent manner in vivo. These results give additional insights into the molecular mechanism of negative regulation of mucin overproduction and enhance our understanding of mucus hypersecretion during airway mucosal inflammation.
MeSH terms
Adenosine Triphosphate/metabolismAnimalsCells, CulturedEpithelial Cells/drug effects*Epithelial Cells/metabolismEpithelial Cells/pathologyGTP-Binding Protein alpha Subunits, Gq-G11/metabolismHumansLipopolysaccharides/isolation & purificationLipopolysaccharides/pharmacology*MetaplasiaMiceMice, Inbred C57BLMice, KnockoutMucin 5AC/geneticsMucin 5AC/metabolism*Nasal Mucosa/drug effectsNasal Mucosa/metabolismPseudomonas aeruginosa/chemistryRGS Proteins/deficiencyRGS Proteins/geneticsRGS Proteins/metabolism*RNA, Messenger/metabolismReceptors, Purinergic P2/drug effectsReceptors, Purinergic P2/metabolismReceptors, Purinergic P2Y2Respiratory Mucosa/drug effects*Respiratory Mucosa/metabolismRespiratory Mucosa/pathologyTime FactorsToll-Like Receptor 4/drug effectsToll-Like Receptor 4/metabolismTransfectionUp-Regulation
DOI
10.1165/rcmb.2008-0280OC
PMID
19059885
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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