Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 413, Issue 4, Pages 499-503Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.08.087
Keywords
Ovarian cancer G-protein-coupled receptor 1; G(q/11) protein; Airway acidification; Connective tissue growth factor; Airway smooth muscle cell
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Funding
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [21390016, 21591158, 22790844, 23591456, 23591916, 23659029] Funding Source: KAKEN
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Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-beta-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G(q/11) protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP3) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G(q/11) protein and inositol-1,4,5-trisphosphate-induced Ca2+ mobilization in human ASMCs. (C) 2011 Elsevier Inc. All rights reserved.
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