Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells
Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells
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DOI：
10.1016/j.bbrc.2011.08.087
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发表时间：
2011-10-07
影响因子：
3.1
通讯作者：
Okajima, Fumikazu
中科院分区：
文献类型：
--
作者：
Matsuzaki, Shinichi;Ishizuka, Tamotsu;Okajima, Fumikazu
哮喘以气道炎症、高反应性和气道重塑为特征。已知细胞外酸化与严重哮喘相关;然而，细胞外酸化在气道重塑中的作用仍然难以捉摸。在本研究中，在人气道平滑肌细胞（ASMCs）中研究了酸化对结缔组织生长因子（CTGF）表达的影响，CTGF是参与细胞外基质蛋白形成和气道重塑的关键因子。酸性pH单独诱导CTGF的大量产生，并增强转化生长因子（TGF）-β诱导的CTGF mRNA和蛋白表达。细胞外酸性pH诱导的作用被抑制的质子敏感卵巢癌G蛋白偶联受体（OGR 1）与其特定的小干扰RNA和G（q/11）蛋白特异性抑制剂，YM-254890，或肌醇-1，4，5-三磷酸（IP 3）受体拮抗剂，2-APB。总之，细胞外酸化通过OGR 1/G（q/11）蛋白和肌醇-1，4，5-三磷酸诱导的人ASMCs中的Ca 2+动员诱导CTGF产生。(C)2011 Elsevier Inc. All rights reserved.
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.