Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells.

Abstract

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)-β-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 (IP(3)) 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 Ca(2+) mobilization in human ASMCs.

• Authors: Shinichi Matsuzaki, Tamotsu Ishizuka, Hidenori Yamada, Yosuke Kamide, Takeshi Hisada, Isao Ichimonji, Haruka Aoki, Masakiyo Yatomi, Mayumi Komachi, Hiroaki Tsurumaki, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Chihiro Mogi, Koichi Sato, Hideaki Tomura, Masatomo Mori, Fumikazu Okajima
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 413 Issue 4 Pg. 499-503 (Oct 07 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21907704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Acids
• CCN2 protein, human
• GPR68 protein, human
• Peptides, Cyclic
• Protons
• RNA, Small Interfering
• Receptors, G-Protein-Coupled
• YM-254890
• Connective Tissue Growth Factor
• Inositol 1,4,5-Trisphosphate
• Calcium

Topics

• Acids (metabolism)
• Airway Remodeling
• Calcium (metabolism)
• Connective Tissue Growth Factor (biosynthesis)
• Humans
• Hydrogen-Ion Concentration
• Inositol 1,4,5-Trisphosphate (pharmacology)
• Lung (cytology, metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Peptides, Cyclic (pharmacology)
• Protons
• RNA, Small Interfering (genetics)
• Receptors, G-Protein-Coupled (genetics, metabolism)