Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism
Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism
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DOI：
10.1016/j.bbamcr.2014.07.009
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发表时间：
2014-11-01
影响因子：
5.1
通讯作者：
Modesti, Pietro Amedeo
中科院分区：
文献类型：
--
作者：
Fiaschi, Tania;Magherini, Francesca;Modesti, Pietro Amedeo
心脏成纤维细胞在糖尿病引起的心肌结构和功能变化中起重要作用。本研究的目的是确定高葡萄糖（单独或补充血管紧张素II）在激活JAK 2/STAT 3通路及其参与心脏成纤维细胞I型胶原蛋白产生中的作用。我们观察到，糖尿病环境1）增强JAK 2和STAT 3的酪氨酸磷酸化; 2）通过活性氧介导的机制诱导酪氨酸磷酸化的STAT 3的核定位，血管紧张素II刺激进一步增强STAT 3的核积聚; 3）刺激胶原蛋白I的产生。在单独或补充外源性血管紧张素II的高糖中，活性氧的耗竭或STAT 3的沉默抑制了这种作用。结合，我们的数据表明，增加胶原蛋白I沉积在设置的高糖发生通过活性氧和STAT 3依赖性机制。我们的研究结果揭示了一个新的作用，STAT 3作为一个关键的信号分子的胶原蛋白I生产在心脏成纤维细胞暴露于糖尿病的环境。(C)2014爱思唯尔有限公司版权所有。
Cardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment. (C) 2014 Elsevier B.V. All rights reserved.