Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing.
Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing.
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DOI：
10.3390/cells10030663
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发表时间：
2021-03-16
期刊：
影响因子：
6
通讯作者：
Peyronnet R
中科院分区：
文献类型：
--
作者：
Emig R;Knodt W;Krussig MJ;Zgierski-Johnston CM;Gorka O;Groß O;Kohl P;Ravens U;Peyronnet R
心肌细胞的力学环境不断变化，并在疾病期间发生重大改变。大多数心脏疾病，包括心房颤动，都伴随着纤维化，这会损害心脏的电和机械功能。纤维化组织的一个关键特征是细胞外基质的过度积累，导致组织硬度增加。已知细胞会对机械环境的变化做出反应，但这种能力背后的分子机制尚未完全了解。我们使用细胞培养系统和具有可调刚度的水凝胶，结合先进的生物物理和成像技术，来阐明拉伸激活通道Piezo 1在人心房成纤维细胞机械传感中的作用。改变Piezo 1的表达水平表明，这种机械传感器有助于细胞骨架的组织，影响人胚肾细胞和人心房成纤维细胞的机械特性。我们的研究结果表明，这种反应是独立的Piezo 1介导的离子传导在质膜上，介导的部分组成部分的整合素途径。此外，我们表明，Piezo 1是有助于成纤维细胞适应基质硬度的变化，和Piezo 1诱导的细胞硬化是通过一种需要白细胞介素-6的信号传导机制，以旁分泌的方式传递给其他细胞。Piezo 1可能是靶向干扰心脏成纤维细胞功能的新候选者。
The mechanical environment of cardiac cells changes continuously and undergoes major alterations during diseases. Most cardiac diseases, including atrial fibrillation, are accompanied by fibrosis which can impair both electrical and mechanical function of the heart. A key characteristic of fibrotic tissue is excessive accumulation of extracellular matrix, leading to increased tissue stiffness. Cells are known to respond to changes in their mechanical environment, but the molecular mechanisms underlying this ability are incompletely understood. We used cell culture systems and hydrogels with tunable stiffness, combined with advanced biophysical and imaging techniques, to elucidate the roles of the stretch-activated channel Piezo1 in human atrial fibroblast mechano-sensing. Changing the expression level of Piezo1 revealed that this mechano-sensor contributes to the organization of the cytoskeleton, affecting mechanical properties of human embryonic kidney cells and human atrial fibroblasts. Our results suggest that this response is independent of Piezo1-mediated ion conduction at the plasma membrane, and mediated in part by components of the integrin pathway. Further, we show that Piezo1 is instrumental for fibroblast adaptation to changes in matrix stiffness, and that Piezo1-induced cell stiffening is transmitted in a paracrine manner to other cells by a signaling mechanism requiring interleukin-6. Piezo1 may be a new candidate for targeted interference with cardiac fibroblast function.
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影响因子：
4
作者：
Farre, Nuria;Jorba, Ignasi;Navajas, Daniel
通讯作者：
Navajas, Daniel
影响因子：
15.9
作者：
FORRESTER, JS;SWAN, HJC;DIAMOND, G
通讯作者：
DIAMOND, G
影响因子：
5.9
作者：
Ellefsen, Kyle L.;Holt, Jesse R.;Pathak, Medha M.
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由机械敏感离子通道 PIEZO1 和组织力学介导的前馈机制促进胶质瘤侵袭。
影响因子：
16.2
作者：
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通讯作者：
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影响因子：
3.4
作者：
Fabry, Ben;Klemm, Anna H.;Goldmann, Wolfgang H.
通讯作者：
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