Increased intracellular Cl- concentration by activating FAK promotes airway epithelial BEAS-2B cells proliferation and wound healing
Increased intracellular Cl- concentration by activating FAK promotes airway epithelial BEAS-2B cells proliferation and wound healing
复制标题
通过激活FAK增加细胞内Cl-浓度促进气道上皮BEAS-2B细胞增殖和伤口愈合
DOI：
10.1016/j.abb.2019.108225
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发表时间：
2020
影响因子：
3.9
通讯作者：
Qin Xiaoqun
中科院分区：
文献类型：
--
作者：
Wang Jia;Luo Jinhua;Huang Wenjie;Liu Caixia;Zeng Dan;Liu Huijun;Qu Xiangping;Liu Chi;Xiang Yang;Qin Xiaoqun
细胞内Cl−浓度（[Cl−]i）的增加可能是气道上皮细胞对各种刺激的一般反应，并可能参与一些基本的细胞功能。然而，细胞的基本功能活动，如增殖和伤口愈合，是否与Cl−活动有关仍不清楚。本研究旨在探讨[Cl−]离子对气道上皮BEAS-2B细胞增殖和创伤愈合能力的影响及其可能机制。BEAS-2B细胞用四种Cl−通道抑制剂（T16 Ainh-A01、CFTRinh-172、CaCCinh-A01和IAA-94）处理，并使用Cl−荧光探针N-（乙氧羰基甲基）-6-甲氧基溴化喹啉。结果表明，所有Cl−通道抑制剂都能增加BEAS-2B细胞中的[Cl−] i。Cl−通道抑制剂或高水平的[Cl−]钳制可诱导[Cl −] i增加，增强黏着斑激酶（FAK）的磷酸化，从而促进BEAS-2B细胞的增殖和伤口愈合能力。相比之下，FAK抑制剂PF 573228消除了由[Cl−]i增加诱导的这些效应。FAK还激活PI 3 K/AKT信号通路。总之，增加的[Cl−] i通过激活FAK来激活PI 3 K/AKT信号通路，从而促进BEAS-2B细胞的增殖和伤口愈合能力。细胞内Cl−可能作为信号分子调节气道上皮细胞的增殖和创伤愈合能力。
An increase in intracellular Cl−concentration ([Cl−]i) may be a general response of airway epithelial cells to various stimuli and may participate in some basic cellular functions. However, whether the basic functional activities of cells, such as proliferation and wound healing, are related to Cl−activities remains unclear. This study aimed to investigate the effects and potential mechanisms of [Cl−]ion the proliferation and wound healing ability of airway epithelial BEAS-2B cells. BEAS-2B cells were treated with four Cl−channel inhibitors (T16Ainh-A01, CFTRinh-172, CaCCinh-A01, and IAA-94), and the Cl−fluorescence probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used. Results showed that all Cl−channel inhibitors could increase [Cl−]iin BEAS-2B cells. The increased [Cl−]iinduced by Cl−channel inhibitors or clamping [Cl−]iat high levels enhanced the phosphorylation of focal adhesion kinase (FAK) and subsequently promoted the proliferation and wound healing ability of BEAS-2B cells. By contrast, the FAK inhibitor PF573228 abrogated these effects induced by the increased [Cl−]i. FAK also activated the PI3K/AKT signaling pathway. In conclusion, increased [Cl−]ipromotes the proliferation and wound healing ability of BEAS-2B cells by activating FAK to activate the PI3K/AKT signaling pathway. Intracellular Cl−may act as a signaling molecule to regulate the proliferation and wound healing ability of airway epithelial cells.