Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle actin filaments during myofibroblast differentiation
Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle actin filaments during myofibroblast differentiation
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DOI：
10.1152/ajplung.00390.2011
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发表时间：
2012-10-01
影响因子：
4.9
通讯作者：
Ding, Qiang
中科院分区：
文献类型：
--
作者：
Cai, Guo-Qiang;Chou, Chu-Fang;Ding, Qiang
蔡国强，周春芳，胡敏，郑安，Reichardt LF，关家龙，方华，Luckhardt TR，周勇，Thannickal VJ，丁强。肌成纤维细胞分化过程中神经元Wiskott-Aldrich综合征蛋白（N-WASP）在α -平滑肌肌动蛋白丝形成中的关键作用。[J] .中国生物医学工程学报，2016,31(2):387 - 398。2012年8月10日首次发表；doi: 10.1152 / ajplung.00390.2011。肌成纤维细胞参与与肺纤维化相关的病理间质反应。完全分化的肌成纤维细胞的一个显著表型标志是含有新合成的α -平滑肌肌动蛋白（α - sma）的聚合的厚细胞质细丝。这些含有α - sma的细胞质细丝在组织重塑过程中对肌成纤维细胞的收缩性很重要。然而，调控含有α - sma的细丝形成和成熟的分子机制尚未明确。这项研究表明，神经元Wiskott-Aldrich综合征蛋白（N-WASP）在肌成纤维细胞分化和肌成纤维细胞收缩过程中调节含有α - sma的细胞质丝的形成中发挥了关键作用。局灶黏附激酶（FAK）被转化生长因子- β 1 （tgf - β 1）激活，是N-WASP酪氨酸残基256 （Y256）磷酸化所必需的。N-WASP的Y256磷酸化对于tgf - β 1诱导的人肺原代成纤维细胞中含有α - sma的细胞质丝的形成至关重要。此外，我们证明了肌动蛋白相关蛋白（Arp） 2/3复合物位于N-WASP的下游，并介导含有α - sma的细胞质细丝的成熟。总之，这项研究支持了N-WASP在整合FAK和Arp2/3信号以介导肌成纤维细胞分化和成熟过程中含有α - sma的细胞质丝的形成中的关键作用。
Cai G-Q, Chou C-F, Hu M, Zheng A, Reichardt LF, Guan J-L, Fang H, Luckhardt TR, Zhou Y, Thannickal VJ, Ding Q. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of alpha-smooth muscle actin filaments during myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol 303: L692-L702, 2012. First published August 10, 2012; doi:10.1152/ajplung.00390.2011.-Myofibroblasts are implicated in pathological stromal responses associated with lung fibrosis. One prominent phenotypic marker of fully differentiated myofibroblasts is the polymerized, thick cytoplasmic filaments containing newly synthesized alpha-smooth muscle actin (alpha-SMA). These alpha-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of alpha-SMA-containing filaments have not been defined. This study demonstrates a critical role for neuronal Wiskott-Aldrich syndrome protein (N-WASP) in regulating the formation of alpha-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-beta 1 (TGF-beta 1) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-beta 1-induced formation of alpha-SMA-containing cytoplasmic filaments in primary human lung fibroblasts. In addition, we demonstrate that actin-related protein (Arp) 2/3 complex is downstream of N-WASP and mediates the maturation of alpha-SMA-containing cytoplasmic filaments. Together, this study supports a critical role of N-WASP in integrating FAK and Arp2/3 signaling to mediate formation of alpha-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation.