Microtopographical features generated by photopolymerization recruit RhoA/ROCK through TRPV1 to direct cell and neurite growth.
Microtopographical features generated by photopolymerization recruit RhoA/ROCK through TRPV1 to direct cell and neurite growth.
复制标题
光聚合产生的微地形特征通过 TRPV1 招募 RhoA/ROCK 来指导细胞和神经突生长。
DOI：
10.1016/j.biomaterials.2015.02.057
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发表时间：
2015-06
期刊：
影响因子：
14
通讯作者：
Hansen, Marlan R.
中科院分区：
文献类型：
--
作者：
Li, Shufeng;Tuft, Bradley W.;Xu, Linjing;Polacco, Marc A.;Clarke, Joseph C.;Guymon, C. Allan;Hansen, Marlan R.
关键词：
细胞过程，包括生长锥，响应于其微环境中的生物物理线索，以建立功能性组织结构和细胞间网络。细胞感知生物物理信号并将其转化为定向生长的机制尚不清楚。我们使用光聚合来制造具有图案化的微观形貌特征的甲基丙烯酸酯平台，该图案化的微观形貌特征精确地引导神经突生长和雪旺细胞排列。瞬时受体电位阳离子通道亚家族V成员1（TRPV 1）的药理学抑制或通过RNAi减少TRPV 1的表达显著地破坏了通过这些微地形特征的神经突引导。TRPV 1的外源性表达诱导NIH 3 T3成纤维细胞的对齐，这些成纤维细胞在TRPV 1不存在的情况下无法对齐，进一步暗示TRPV 1通道是细胞对生物物理信号应答的关键介质。Microtopographic功能增加RhoA活性在生长锥和TRPV 1表达NIH 3 T3细胞。此外，Rho相关激酶（ROCK）磷酸化在微图案化表面上的生长锥和神经突中升高。通过药理学化合物抑制RhoA/ROCK或通过RNAi减少ROCKI或ROCKII同种型的表达废除了神经突和细胞排列，证实RhoA/ROCK信号传导介导神经突和细胞排列到微地形特征。这些研究表明，微地形线索招募TRPV 1通道和下游信号通路，包括RhoA和ROCK，指导神经突和细胞生长。
Cell processes, including growth cones, respond to biophysical cues in their microenvironment to establish functional tissue architecture and intercellular networks. The mechanisms by which cells sense and translate biophysical cues into directed growth are unknown. We used photopolymerization to fabricate methacrylate platforms with patterned microtopographical features that precisely guide neurite growth and Schwann cell alignment. Pharmacologic inhibition of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or reduced expression of TRPV1 by RNAi significantly disrupts neurite guidance by these microtopographical features. Exogenous expression of TRPV1 induces alignment of NIH3T3 fibroblasts that fail to align in the absence of TRPV1, further implicating TRPV1 channels as critical mediators of cellular responses to biophysical cues. Microtopographic features increase RhoA activity in growth cones and in TRPV1-expressing NIH3T3 cells. Further, Rho-associated kinase (ROCK) phosphorylation is elevated in growth cones and neurites on micropatterned surfaces. Inhibition of RhoA/ROCK by pharmacological compounds or reduced expression of either ROCKI or ROCKII isoforms by RNAi abolishes neurite and cell alignment, confirming that RhoA/ROCK signaling mediates neurite and cell alignment to microtopographic features. These studies demonstrate that microtopographical cues recruit TRPV1 channels and downstream signaling pathways, including RhoA and ROCK, to direct neurite and cell growth.
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影响因子：
2.8
作者：
Clarke, Joseph C.;Tuft, Bradley W.;Clinger, John D.;Levine, Rachel;Figueroa, Lucas Sievens;Guymon, C. Allan;Hansen, Marlan R.
通讯作者：
Hansen, Marlan R.
影响因子：
14
作者：
Johansson, F;Carlberg, P;Kanje, M
通讯作者：
Kanje, M
影响因子：
7.2
作者：
Bashaw, Greg J.;Klein, Ruediger
通讯作者：
Klein, Ruediger
影响因子：
64.8
作者：
Li, Y;Jia, YC;Yuan, XB
通讯作者：
Yuan, XB
影响因子：
2.1
作者：
Hassepass, Frederike;Bulla, Stefan;Aschendorff, Antje
通讯作者：
Aschendorff, Antje