P2X7 Receptor Deficiency Ameliorates STZ-induced Cardiac Damage and Remodeling Through PKCβ and ERK

Frontiers in Cell and Developmental Biology

Li Li¹  Shanjun Huang²  Yonghua Wang³  Yihan Zhao⁴  Weiqi Wang⁴  Zhouqing Huang⁴  Ting Wang⁴  Ya Lin⁴  Weijian Huang⁴ 

[1] Department of Anesthesiology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China;Department of Cardiology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China;Department of Physical Education, Wenzhou Medical University, Wenzhou, China;The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;

关键词: diabetic cardiomyopathy;    P2X7 receptor;    cardiac remodeling;    PKCβ;    ERK;   

DOI  :  10.3389/fcell.2021.692028

来源: DOAJ

【 摘 要 】

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus which result in cardiac remodeling and subsequent heart failure. However, the role of P2X7 receptor (P2X7R) in DCM has yet to be elucidated. The principal objective of this study was to investigate whether P2X7R participates in the pathogenesis of DCM. In this study, the C57BL/6 diabetic mouse model was treated with a P2X7R inhibitor (A438079). Cardiac dysfunction and remodeling were attenuated by the intraperitoneal injection of A438079 or P2X7R deficiency. In vitro, A438079 reduced high glucose (HG) induced cell damage in H9c2 cells and primary rat cardiomyocytes. Furthermore, HG/streptozotocin (STZ)-induced P2X7R activation mediated downstream protein kinase C-β (PKCβ) and extracellular regulated protein kinases (ERK) activation. This study provided evidence that P2X7R plays an important role in the pathogenesis of STZ-induced diabetic cardiac damage and remodeling through the PKCβ/ERK axis and suggested that P2X7R might be a potential target in the treatment of diabetic cardiomyopathy.

【 授权许可】

Unknown