Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury.
Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury.
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蜗牛1在心脏肌纤维细胞中的作用对于低氧损伤后心脏纤维化很重要。
DOI：
10.1371/journal.pone.0162636
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Longmore GD
中科院分区：
文献类型：
--
作者：
Biswas H;Longmore GD
心脏的低血压损伤导致心脏纤维化，从而导致心脏功能障碍和心力衰竭。SNAIL 1是一种锌指转录因子，与器官损伤和癌症后的纤维化有关。为了确定SNAIL 1的作用是否有助于缺氧损伤后的心脏纤维化，我们使用了内源性SNAIL 1生物发光报告小鼠和SNAIL 1敲除小鼠模型。在这里，我们报告说，SNAIL 1的表达上调，在梗死的心脏，特别是在肌成纤维细胞。在离体培养中利用原代心脏成纤维细胞，我们发现促纤维化因子和胶原蛋白I增加SNAIL 1蛋白水平。SNAIL 1在心脏成纤维细胞中是肌成纤维细胞命运、胶原蛋白I表达和纤维化相关基因表达所必需的。总之，这些数据表明，SNAIL 1表达在缺氧损伤后的心脏成纤维细胞中被诱导，并有助于肌成纤维细胞表型和纤维化瘢痕形成。瘢痕中的所得胶原沉积可维持肌成纤维细胞中升高的SNAIL 1表达并有助于传播纤维化。
Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis.
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影响因子：
7.8
作者：
Rowe, R. Grant;Li, Xiao-Yan;Hu, Yuexian;Saunders, Thomas L.;Virtanen, Ismo;de Herreros, Antonio Garcia;Becker, Karl-Friedrich;Ingvarsen, Signe;Engelholm, Lars H.;Bommer, Guido T.;Fearon, Eric R.;Weiss, Stephen J.
通讯作者：
Weiss, Stephen J.
影响因子：
82.9
作者：
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通讯作者：
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影响因子：
5.6
作者：
O'Connor, Joseph W.;Riley, Patrick N.;Gomez, Esther W.
通讯作者：
Gomez, Esther W.
DOI：
10.1073/pnas.0805038105
发表时间：
2008-09-02
影响因子：
11.1
作者：
van Rooij, Eva;Sutherland, Lillian B.;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
50.3
作者：
Hsu, Dennis Shin-Shian;Wang, Hsiao-Jung;Yang, Muh-Hwa
通讯作者：
Yang, Muh-Hwa