Cardiac stem cells transplantation enhances the expression of connexin 43 via the ANG II/AT1R/TGF-beta1 signaling pathway in a rat model of myocardial infarction
Cardiac stem cells transplantation enhances the expression of connexin 43 via the ANG II/AT1R/TGF-beta1 signaling pathway in a rat model of myocardial infarction
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心脏干细胞移植通过ANG II/AT1R/TGF-β1信号通路增强心肌梗死大鼠模型中连接蛋白43的表达
DOI：
10.1016/j.yexmp.2015.11.013
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发表时间：
2015-12-01
影响因子：
3.6
通讯作者：
Wang, Tong
中科院分区：
文献类型：
--
作者：
Hou, Jingying;Yan, Ping;Wang, Tong
背景资料：在这项研究中，我们假设，CSC介导的表达Cx43移植后MI通过ANG II/AT 1 R/TGF-β 1信号pathway.Methods：心肌梗死（MI）诱导在20只雄性SD大鼠。将大鼠随机分为两组，然后在MI后两周将5 × 106个磷酸盐缓冲液（PBS）中的PKH 26标记的CSC或等量的PBS单独注射到梗死的前心室游离壁中。结果：CSCs组大鼠左心室不同部位Cx43表达均明显增加（P < 0.01）;血浆及左室不同部位心肌组织血管紧张素Ⅱ（ANG Ⅱ）水平明显降低（P < 0.05; P < 0.01）。血管紧张素Ⅱ Ⅰ型受体（AT 1 R）表达降低，而血管紧张素Ⅱ Ⅱ型受体（AT 2 R）表达增强（P < 0.01）。转化生长因子β 1（TGF-β 1）表达下调（P < 0.01）。母鼠抗十肢麻痹同源物（SMAD）蛋白SMAD 2、SMAD 3表达减弱，SMAD 7表达增强（P < 0.01，P < 0.01，P < 0.05）。此外，心肌梗死后细胞外激酶1/2（ERK 1/2）和p38等丝裂原活化蛋白激酶（MAPK）的表达也明显降低（P < 0.01）。它们可能通过干预ANGII/AT 1 R/TGF-β 1信号通路来调节Cx43的表达。(C)2015 Elsevier Inc. All rights reserved.
Background: In this study, we hypothesized that CSCs mediated the expression of Cx43 after transplantation post MI via the ANG II/AT1R/TGF-beta1 signaling pathway.Methods: Myocardial infarction (MI) was induced in twenty male Sprague-Dawley rats. The rats were randomized into two groups and were then received the injection of 5 x 10(6) CSCs labeled with PKH26 in phosphate buffer solution (PBS) or equal PBS alone into the infarct anterior ventricular free wall two weeks after MI. Six weeks later, relevant signaling molecules involved were all examined.Results: In the CSCs group, an increased expression of Cx43 could be observed in different zones of the left ventricle (P < 0.01). There was a significant reduction of the angiotensin II (ANG II) level in plasma and different regions of the left ventricular cardiac tissues (P < 0.05; P < 0.01). The angiotensin II type I receptor (AT1R) was decreased accompanied with an enhanced expression of angiotensin II type II receptor (AT2R) (P < 0.01). Transforming growth factor beta-1(TGF-beta1) was downregulated (P < 0.01). The expression of mothers against decapentaplegic homolog (SMAD) proteins including SMAD2 and SMAD3 was attenuated whereas SMAD7 was elevated (P < 0.01, P < 0.01, P < 0.05). In addition, the expression of mitogen-activated protein kinases (MAPKs) including extracellular kinases 1/2 (ERK1/2) and p38 was also found to be reduced (P < 0.01).Conclusion: CSCs transplantation could enhance the level of Cx43 after MI. They might function through intervening the ANGII/AT1R/TGF-beta1 signaling pathway to regulate the expression of Cx43. (C) 2015 Elsevier Inc. All rights reserved.