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

TANG Fu-Cai, WANG Hong-Yan, MA Ming-Ming, GUAN Tian-Wang, PAN Long, YAO Dun-Chen, CHEN Ya-Lan, CHEN Wei-Bei, TU Yong-Sheng, FU Xiao-Dong

Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079；Department of Physiology, School of Basic Sciences； The First Clinical Medical College； Department of Pathology, School of Basic Sciences； The Second Clinical Medical College； The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 510182, China； Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China

Abstract

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.

Key words: CD147; cyclophilin A; cardiac hypertrophy; hypertension

Received: 2015-03-09　　Accepted: 2015-05-27

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Citing This Article：

TANG Fu-Cai, WANG Hong-Yan, MA Ming-Ming, GUAN Tian-Wang, PAN Long, YAO Dun-Chen, CHEN Ya-Lan, CHEN Wei-Bei, TU Yong-Sheng, FU Xiao-Dong. CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy. Acta Physiol Sin 2015; 67 (4): 393-400 (in Chinese with English abstract).