Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts
Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts
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DOI：
10.1016/j.bbrc.2014.09.063
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发表时间：
2014-10-10
影响因子：
3.1
通讯作者：
Hasegawa, Yoshinori
中科院分区：
文献类型：
--
作者：
Murata, Naohiko;Ito, Satoru;Hasegawa, Yoshinori
进行性肺纤维化的一个原因是特发性肺纤维化和严重急性呼吸窘迫综合征患者肺部炎症或损伤后创面愈合失调。机械力被认为通过激活肺成纤维细胞来调节肺纤维化。本研究观察了机械牵张对人肺成纤维细胞内钙离子浓度([Ca~(2+)](I))和三磷酸腺苷(ATP)释放的影响。使用拉伸装置对培养在涂有I型胶原的硅胶室中的成纤维细胞施加单轴拉伸(应变为10-30%)。在拉伸和随后的卸载后，[Ca~(2+)](I)以应变依赖的方式瞬时增加。引起质膜拉伸的低渗胁迫也使细胞内[Ca~(2+)]一过性升高。(1)在无Ca~(2+)溶液中，拉伸引起的[Ca~(2+)]升高幅度减弱。相反，20%拉伸引起的[Ca~(2+)](I)升高不能被拉伸激活通道的抑制剂GsMTx-4、Gd3+、Ru红或细胞松弛素D所抑制。然而，ATP二磷酸水解酶apyrase或嘌呤受体拮抗剂苏拉明不能抑制牵张引起的[Ca~(2+)](I)升高。综上所述，机械拉伸可独立于传统的拉伸敏感离子通道--肌动蛋白细胞骨架--诱导钙内流，并释放三磷酸腺苷。(C)2014 Elsevier Inc.保留所有权利。
One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca2+ concentration ([Ca2+](i)) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10-30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca2+](i) transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca2+](i) The stretch-induced [Ca2+](i) elevation was attenuated in Ca2+-free solution. In contrast, the increase of [Ca2+](i) by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd3+, ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca2+](i) elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca2+ influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP. (C) 2014 Elsevier Inc. All rights reserved.