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Cardiac Specific Overexpression of hHole Attenuates Isoproterenol–Induced Hypertrophic Remodeling through Inhibition of Extracellular Signal-Regulated Kinases (ERKs) Signalling

[ Vol. 16 , Issue. 5 ]

Author(s):

W. Xu, Y. Wang, J. Zhou, X. Zhu, S. Zhang, W. Yuan, X. Liu, Y. Shi, L. Cao, Q. Zeng, Z. Jiang, X. Ye, Y. Wan, X. Peng, Y. Deng, F. Chen, X. Wang, G. Dai, S. Luo, X. Fan, X. Mo, X. Wu and Y. Li   Pages 515 - 523 ( 9 )

Abstract:


The human Hole gene (hHole) encodes a six-transmembrane protein with 319- amino acids. Our previous study showed that hHole was strongly expressed in adult heart and may act as a suppressor of extracellular signal-regulated kinases (ERKs), overactivation of which contributed to pathological cardiac hypertrophy. In this study, it was observed that Hole expression was up-regulated in murine hypertrophic hearts. In a cardiac specific transgenic mouse model, it was observed that overexpression of hHole specifically in heart attenuated cardiac hypertrophy and fibrosis induced by isoproterenol (ISO), with blunted transcriptions of ERK1/2, total ERK1/2 proteins and phosphorylated ERK1/2 (p-ERK1/2) levels. Furthermore, overexpression of hHole in mice by hydrodynamic tail-vein injection with hHole plamids also inhibited cardiac hypertrophy induced by ISO. Our work identified hHole as a novel repressor of cardiac hypertrophy, and provided new insights into the possible target for the prevention or treatment of cardiac diseases.

Keywords:

Cardiac hypertrophy, human Hole gene (hHole), isoproterenol (ISO), extracellular signal-regulated kinases (ERKs).

Affiliation:

The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha 410081, China.



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