The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment of alveolar epithelial cells.
The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment of alveolar epithelial cells.
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DOI：
10.1371/journal.pone.0089429
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Schwingshackl A
中科院分区：
文献类型：
--
作者：
Roan E;Waters CM;Teng B;Ghosh M;Schwingshackl A
急性呼吸窘迫综合征仍然具有挑战性，部分原因是对潜在机制知之甚少。虽然炎症和屏障功能丧失与疾病进展相关，但我们对呼吸机相关肺损伤相关生物物理机制的理解尚不完整。在这种思路下，我们最近发现，在F-肌动蛋白含量和变形的AEC的变化导致细胞脱离机械拉伸。在其他地方，我们发现，细胞因子的分泌和增殖的调节部分由拉伸激活的2孔结构域K+（K2 P）通道TREK-1在肺泡上皮细胞（AEC）。因此，本研究的目的是确定TREK-1是否通过细胞骨架重塑和细胞脱离来调节AEC的机械生物学。使用TREK-1缺陷的人AEC系（A549），我们通过共聚焦显微镜检查细胞骨架，并定量F-肌动蛋白含量的差异。我们使用纳米压痕与原子力显微镜来测量细胞的变形能力和分离测定来量化我们的单层损伤水平。我们发现与对照细胞相比，TREK-1缺陷细胞中F-肌动蛋白减少，变形能力增加。尽管总黏着斑蛋白和粘着斑激酶（FAK）水平保持不变，但粘着斑似乎不太突出，并且TREK-1缺陷细胞中Tyr 925残基处的FAK磷酸化程度更高。TREK-1缺陷细胞具有更少的F-肌动蛋白，并且更易变形，使它们更能抵抗拉伸诱导的损伤。
Acute Respiratory Distress Syndrome remains challenging partially because the underlying mechanisms are poorly understood. While inflammation and loss of barrier function are associated with disease progression, our understanding of the biophysical mechanisms associated with ventilator-associated lung injury is incomplete. In this line of thinking, we recently showed that changes in the F-actin content and deformability of AECs lead to cell detachment with mechanical stretch. Elsewhere, we discovered that cytokine secretion and proliferation were regulated in part by the stretch-activated 2-pore domain K+ (K2P) channel TREK-1 in alveolar epithelial cells (AECs). As such, the aim of the current study was to determine whether TREK-1 regulated the mechanobiology of AECs through cytoskeletal remodeling and cell detachment. Using a TREK-1-deficient human AEC line (A549), we examined the cytoskeleton by confocal microscopy and quantified differences in the F-actin content. We used nano-indentation with an atomic force microscope to measure the deformability of cells and detachment assays to quantify the level of injury in our monolayers. We found a decrease in F-actin and an increase in deformability in TREK-1 deficient cells compared to control cells. Although total vinculin and focal adhesion kinase (FAK) levels remained unchanged, focal adhesions appeared to be less prominent and phosphorylation of FAK at the Tyr925 residue was greater in TREK-1 deficient cells. TREK-1 deficient cells have less F-actin and are more deformable making them more resistant to stretch-induced injury.
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影响因子：
3.3
作者：
Deramaudt TB;Dujardin D;Hamadi A;Noulet F;Kolli K;De Mey J;Takeda K;Rondé P
通讯作者：
Rondé P
影响因子：
4.8
作者：
Katz, BZ;Romer, L;Yamada, KM
通讯作者：
Yamada, KM
DOI：
10.1111/j.1365-2613.2012.00823.x
发表时间：
2012-08-01
影响因子：
3
作者：
Nagato, Akinori C.;Bezerra, Frank S.;Valenca, Samuel S.
通讯作者：
Valenca, Samuel S.
影响因子：
1.6
作者：
Delong, Peter;Murray, James A.;Cook, Christopher K.
通讯作者：
Cook, Christopher K.
影响因子：
8.8
作者：
Meng, X. N.;Jin, Y.;Yu, Y.;Bai, J.;Liu, G. Y.;Zhu, J.;Zhao, Y. Z.;Wang, Z.;Chen, F.;Lee, K-Y;Fu, S. B.
通讯作者：
Fu, S. B.