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

被引:27
作者
Song, Kyoung Seob [1 ,2 ]
Kim, Hyun Jun [5 ]
Kim, Kyubo
Lee, Jeung Gweon
Yoon, Joo-Heon [1 ,2 ,3 ,4 ]
机构
[1] Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Med, Airway Mucus Inst, Seoul 120752, South Korea
[3] Yonsei Univ, Coll Med, Brain Korea Med Sci 21, Seoul 120752, South Korea
[4] Yonsei Univ, Coll Med, Res Ctr Human Nat Def Syst, Seoul 120752, South Korea
[5] Ajou Univ, Coll Med, Dept Otolaryngol, Suwon 441749, South Korea
关键词
lipopolysaccharide; ATP; MUC5AC; P2Y(2); RGS4; EPITHELIAL-CELLS; CYSTIC-FIBROSIS; DIFFERENTIAL REGULATION; MUCIN EXPRESSION; GENE-EXPRESSION; RELEASE; ACTIVATION; LIPOPOLYSACCHARIDE; INTERLEUKIN-1-BETA; ENDOTOXIN;
D O I
10.1165/rcmb.2008-0280OC
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 LIPS 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 MUCSAC 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.
引用
收藏
页码:40 / 49
页数:10
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