Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells |
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| Authors: | Matsuzaki Shinichi Ishizuka Tamotsu Yamada Hidenori Kamide Yosuke Hisada Takeshi Ichimonji Isao Aoki Haruka Yatomi Masakiyo Komachi Mayumi Tsurumaki Hiroaki Ono Akihiro Koga Yasuhiko Dobashi Kunio Mogi Chihiro Sato Koichi Tomura Hideaki Mori Masatomo Okajima Fumikazu |
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| Institution: | aDepartment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan;bLaboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan;cGunma University Graduate School of Health Sciences, Maebashi 371-8511, Japan |
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| 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 Gq/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/Gq/11 protein and inositol-1,4,5-trisphosphate-induced Ca2+ mobilization in human ASMCs. |
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| Keywords: | Abbreviations: CTGF connective tissue growth factor ASMCs airway smooth muscle cells TGF-β transforming growth factor-β OGR1 ovarian cancer G-protein-coupled receptor 1 GPCRs G protein coupled receptors ECM extracellular matrix siRNA small interfering RNA LPA1 lysophosphatidic acid receptor 1 ERK extracellular signal-regulated kinase MAPK mitogen-activated protein kinase IP3 inositol-1 4 5-trisphosphate |
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