Whole animal knockout of smooth muscle alpha-actin does not alter excisional wound healing or the fibroblast-to-myofibroblast transition
Whole animal knockout of smooth muscle alpha-actin does not alter excisional wound healing or the fibroblast-to-myofibroblast transition
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DOI：
10.1111/wrr.12001
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Howard, Eric W.
中科院分区：
文献类型：
--
作者：
Tomasek, James J.;Haaksma, Carol J.;Howard, Eric W.
肌成纤维细胞的收缩表型和功能被认为在伤口愈合中起关键作用。据推测，平滑肌a-肌动蛋白在肌成纤维细胞中的表达对其形成和功能至关重要。我们用平滑肌a-肌动蛋白缺失的小鼠来验证这一假设。在平滑肌-肌动蛋白缺失和野生型小鼠中，全层切除伤口愈合的速度相似。此外，在平滑肌α -肌动蛋白缺失的肉芽组织中，当用识别所有肌动蛋白同种异型的单克隆抗体进行免疫染色时，成纤维细胞表现出肌成纤维细胞样分布和应激纤维样模式，表明这些细胞获得了肌成纤维细胞表型。平滑肌α -肌动蛋白缺失小鼠和野生型小鼠的真皮成纤维细胞形成应激纤维和超成熟的局灶粘连，并在转化生长因子- β 1的作用下产生相似的收缩力。通过免疫染色、实时聚合酶链反应和质谱分析显示，平滑肌-肌动蛋白和骨骼肌-肌动蛋白在平滑肌-肌动蛋白缺失的肌成纤维细胞中表达。这些结果表明，平滑肌a-肌动蛋白对肌成纤维细胞的形成和功能以及伤口愈合不是必需的，平滑肌-肌动蛋白和骨骼肌α -肌动蛋白可能能够在功能上弥补肌成纤维细胞中平滑肌a-肌动蛋白的缺乏。
The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in wound closure. It has been hypothesized that smooth muscle a- actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle a-actin-null mice to test this hypothesis. Full-thickness excisional wounds closed at a similar rate in smooth muscle alpha-actin-null and wild-type mice. In addition, fibroblasts in smooth muscle alpha-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, showing that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle alpha-actin-null and wild-type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-beta 1. Smooth muscle gamma-actin and skeletal muscle alpha-actin were expressed in smooth muscle alpha-actin-null myofibroblasts, as shown by immunostaining, real-time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle a-actin is not necessary for myofibroblast formation and function and for wound closure, and that smooth muscle gamma-actin and skeletal muscle alpha-actin may be able to functionally compensate for the lack of smooth muscle a-actin in myofibroblasts.