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Regulator of G-Protein Signaling 4 Suppresses LPS-Induced MUC5AC Overproduction in the Airway

Authors: Kyoung Seob, Song; Hyun Jun, Kim; Kyubo, Kim; Jeung Gweon, Lee; Joo-Heon, Yoon;

Regulator of G-Protein Signaling 4 Suppresses LPS-Induced MUC5AC Overproduction in the Airway

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.

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Keywords

Lipopolysaccharides, Time Factors, Adenosine Triphosphate/metabolism, Mucin 5AC/genetics, RGS4, Respiratory Mucosa/pathology, Messenger/metabolism, Mucin 5AC, Inbred C57BL, Receptors, Purinergic P2Y2, Mice, Adenosine Triphosphate, Epithelial Cells/pathology, RGS Proteins/genetics, Receptors, Cells, Cultured, Mice, Knockout, Cultured, Gq-G11/metabolism, Respiratory Mucosa/drug effects*, lipopolysaccharide, Nasal Mucosa/drug effects, Epithelial Cells/metabolism, GTP-Binding Protein alpha Subunits, Up-Regulation, Mucin 5AC/metabolism*, Respiratory Mucosa/metabolism, Pseudomonas aeruginosa, RGS Proteins/metabolism*, 570, Cells, Knockout, Epithelial Cells/drug effects*, Respiratory Mucosa, Lipopolysaccharides/pharmacology*, Purinergic P2/drug effects, Transfection, P2Y2, Toll-Like Receptor 4/drug effects, Animals, Humans, RNA, Messenger, Purinergic P2Y2, Lipopolysaccharides/isolation & purification, Pseudomonas aeruginosa/chemistry, Metaplasia, Purinergic P2/metabolism, Receptors, Purinergic P2, Epithelial Cells, MUC5AC, Nasal Mucosa/metabolism, ATP, Mice, Inbred C57BL, Nasal Mucosa, Toll-Like Receptor 4/metabolism, RNA, GTP-Binding Protein alpha Subunits, Gq-G11, RGS Proteins/deficiency, RGS Proteins

  • BIP!
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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    28
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
28
Average
Top 10%
Top 10%
Green
bronze