CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy.

CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy.
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CyPA-CD147-ERK1/2-cyclin D2 信号通路在大鼠左心室肥厚期间上调。

DOI:
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发表时间:
2015-08
期刊:
Sheng Li Xue Bao
影响因子:
--
通讯作者:
Fu, Xiao-Dong
Fu, Xiao-Dong
中科院分区:
其他
文献类型:
--
作者:
Chen, Ya-Lan;Chen, Wei-Bei;Tu, Yong-Sheng;Fu, Xiao-Dong

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心肌肥厚过程中血清亲环蛋白A (CyPA)及其受体CD147及其下游信号通路的变化尚不清楚。本研究旨在探讨CyPA-CD147-ERK1/2-cyclin D2信号通路与心肌肥厚发生的关系。采用2肾2夹法制备大鼠左心室肥厚,分别观察1周、4周和8周。采用左室心重/体重比(LVW/BW)和心肌细胞横截面积(CSA)评价左室肥厚。采用大鼠CyPA酶联免疫吸附测定试剂盒测定血清中CyPA水平。Western blot和免疫染色法检测左心室肌细胞中CyPA、CD147、phospho-ERK1/2和cyclin D2的表达。与假手术组相比,2K2C组4周收缩压达到高血压水平。2K2C组的LVW/BW和CSA在剪后4周和8周显著升高。ELISA结果显示血清CyPA水平显著升高与左心室肥厚程度相关。Western blot结果显示,随着心肌肥厚的发生,左心室组织中CyPA、CD147、phospho-ERK1/2和cyclin D2的表达也显著升高。本研究结果表明,随着左室肥厚的发生,左室组织中血清CyPA和CyPA- cd147 - erk1 /2-cyclin D2信号通路发生时间依赖性上调和激活。这些数据提示CyPA- cd147信号级联可能在左室肥厚的发病机制中发挥作用,CyPA可能是左室肥厚程度的一个预后指标。
The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.
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