title: 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: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors: Shinichi
authors: S
authors: Matsuzaki
authors: Tamotsu
authors: T
authors: Ishizuka
authors: Hidenori
authors: H
authors: Yamada
authors: Yosuke
authors: Y
authors: Kamide
authors: Takeshi
authors: T
authors: Hisada
authors: Isao
authors: I
authors: Ichimonji
authors: Haruka
authors: H
authors: Aoki
authors: Masakiyo
authors: M
authors: Yatomi
authors: Mayumi
authors: M
authors: Komachi
authors: Hiroaki
authors: H
authors: Tsurumaki
authors: Akihiro
authors: A
authors: Ono
authors: Yasuhiko
authors: Y
authors: Koga
authors: Kunio
authors: K
authors: Dobashi
authors: Chihiro
authors: C
authors: Mogi
authors: Koichi
authors: K
authors: Sato
authors: Hideaki
authors: H
authors: Tomura
authors: Masatomo
authors: M
authors: Mori
authors: Fumikazu
authors: F
authors: Okajima
mesh_terms: D000143:Acids / Q000378:metabolism; D056151:Airway Remodeling; D002118:Calcium / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011522:Protons; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D000143:Acids; C526317:CCN2 protein, human; C486281:GPR68 protein, human; D010456:Peptides, Cyclic; D011522:Protons; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C475455:YM-254890; D055513:Connective Tissue Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium