Real-Time Monitoring of the Effects of Telmisartan on Angiotensin II-Induced Mechanical Changes in Live Mesangial Cells Using Atomic Force Microscopy
Real-Time Monitoring of the Effects of Telmisartan on Angiotensin II-Induced Mechanical Changes in Live Mesangial Cells Using Atomic Force Microscopy
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DOI：
10.1159/000339175
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Lee, Sang-Ho
中科院分区：
文献类型：
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作者：
Jeong, Kyung-Hwan;Lee, Tae-Won;Lee, Sang-Ho
背景/目标：最近的研究表明，血管紧张素II（Ang II）1型受体阻滞剂（ARB）可能提供肾脏保护，而不依赖于其降压作用。然而，这方面的证据来自间接方法，如遗传或蛋白质表达研究。在这项研究中，我们假设，替米沙坦，一个特定的ARB，应用于血管紧张素II刺激的系膜细胞（MC）将发挥肾脏保护作用，通过调制MC的机械性能。研究方法：我们利用实时原子力显微镜（AFM）成像和力-距离曲线测量研究了替米沙坦对血管紧张素II诱导的MCs变化的影响。结果如下：实时原子力显微镜图像显示，活MC的细胞收缩后，血管紧张素II暴露的中心，和替米沙坦治疗消除这种变化。细胞弹簧常数显示，替米沙坦阻止了Ang II诱导的MC硬化（Ang II：0.109 +/- 0.019 N/m，Ang II +替米沙坦：0.051 +/- 0.016 N/m，p < 0.005）。与对照组相比，替米沙坦处理的MC具有显著更低的粘附力（对照：0.49 +/- 0.22 nN，替米沙坦：0.22 +/- 0.06 nN，Ang II：0.40 +/-0.25 nN，Ang II +替米沙坦：0.27 +/- 0.14 nN，p < 0.005）。这些结果表明，血管紧张素II刺激的MC的动态收缩和机械性能恢复替米沙坦。结论：我们首次报告使用AFM力-距离曲线对活MC直接监测表面粘附和刚度的变化后，替米沙坦在真实的时间处理的细胞。版权所有（C）2012 S. Karger AG，巴塞尔
Background/Aims: Recent studies have shown that angiotensin II (Ang II) type 1 receptor blockers (ARB) may provide renal protection independent of their blood pressure-lowering effect. However, evidence for this comes from indirect methods, such as genetic or protein expression studies. In this study, we hypothesized that telmisartan, a specific ARB, applied to Ang II-stimulated mesangial cell (MC) would exert a renoprotective effect via modulation of MCs' mechanical properties. Methods: We investigated the effect of telmisartan on Ang II-induced changes in MCs utilizing real-time atomic force microscopy (AFM) imaging and force-distance curve measurements. Results: Real-time AFM images of live MCs demonstrated that cells contracted towards the center after Ang II exposure, and telmisartan treatment abolished this change. Cellular spring constants showed that telmisartan prevented Ang II-induced MC stiffening (Ang II: 0.109 +/- 0.019 N/m, Ang II + telmisartan: 0.051 +/- 0.016 N/m, p < 0.005). Telmisartan-treated MCs had a significantly lower adhesion force than those of the control group (control: 0.49 +/- 0.22 nN, telmisartan: 0.22 +/- 0.06 nN, Ang II: 0.40 +/- 0.25nN, Ang II + telmisartan: 0.27 +/- 0.14 nN, p < 0.005). These results demonstrate that the dynamic contraction and mechanical properties of Ang II-stimulated MCs are restored by telmisartan. Conclusions: We report for the first time the use of AFM force-distance curves on live MCs to directly monitor changes in surface adhesion and stiffness of cells after treatment with telmisartan in real time. Copyright (C) 2012 S. Karger AG, Basel