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06 August 2017 : Laboratory Research  

Platelet Derived Growth Factor Alpha (PDGFRα) Induces the Activation of Cardiac Fibroblasts by Activating c-Kit

Lexun Wang1ABCDEFG, Yuan Yue1BCD, Xiao Yang2CEF, Tian Fan3CEF, Bo Mei1EF, Jian Hou1BCD, Mengya Liang1ABE, Guangxian Chen1AEF, Zhongkai Wu1AG*

DOI: 10.12659/MSM.906038

Med Sci Monit 2017; 23:3808-3816


BACKGROUND: Enhanced platelet-derived growth factor receptor a (PDGFRα) signaling pathway activity leads to cardiac fibrosis. However, because of the pleiotropic effects of PDGFR signaling, its role in mediating the cardiac fibrotic response remains poorly understood. This study aimed to investigate the regulatory effect of c-Kit in cardiac fibroblasts activated by PDGFRa signaling.

MATERIAL AND METHODS: A cardiac fibrosis mice model was induced using isoproterenol, and the heart tissues of mice were tested through western blotting and real-time quantitative PCR (RT-qPCR). The cardiac fibroblasts of neonatal mice were treated with PDGF-AA or transfected with small interfering RNAs (siRNAs) specific for the mouse c-Kit gene. The levels of collagen I, collagen III, and alpha-smooth muscle actin (α-SMA) were analyzed using western blotting and RT-qPCR.

RESULTS: In the heart of the cardiac fibrosis mice model, the activity of c-Kit was enhanced. PDGF-AA treatment accelerated the activity of c-Kit in cardiac fibroblasts. In addition, imatinib inhibited the activity of c-Kit in vivo and in vitro. Moreover, inhibition of c-Kit by siRNAs reduced the expression of α-SMA and collagens in the activated cardiac fibroblasts. Furthermore, PDGFRa directly bound c-Kit in cardiac fibroblasts and stimulated the expression of stem cell factor (SCF).

CONCLUSIONS: Our data demonstrated that PDGF/PDGFRa induced the activation of cardiac fibroblasts by activating c-Kit. This study indicated that c-Kit could be used as a potential therapeutic target for treatment of cardiac fibrosis.

Keywords: Fibroblasts, Proto-Oncogene Proteins c-kit, Receptor, Platelet-Derived Growth Factor alpha, Ventricular Remodeling

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Med Sci Monit 2024; 30:e943911


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750