한빛사논문
- 조회752
Emmanouil Tampakakis1,*, Harshi Gangrade1, Stephanie Glavaris2, Myo Htet1, Sean Murphy1,3,4, Brian Leei Lin1, Ting Liu1, Amir Saberi1, Matthew Miyamoto1,3,4, William Kowalski5, Yoh-Suke Mukouyama5, Gabsang Lee4,6, Liliana Minichiello7, Chulan Kwon1,3,4,*
1Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. 2Division of Paediatric Oncology, Department of Paediatrics, Johns Hopkins University, Baltimore, MD 21205, USA. 3Department of Biomedical Engineering, Department of Cell Biology, Cellular, and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 4Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 5Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. 6Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 7Department of Pharmacology, Oxford University, Oxford, UK.
*Corresponding author.
Abstract
Neurons can regulate the development, pathogenesis, and regeneration of target organs. However, the role of neurons during heart development and regeneration remains unclear. We genetically inhibited sympathetic innervation in vivo, which resulted in heart enlargement with an increase in cardiomyocyte number. Transcriptomic and protein analysis showed down-regulation of the two clock gene homologs Period1/Period2 (Per1/Per2) accompanied by up-regulation of cell cycle genes. Per1/Per2 deletion increased heart size and cardiomyocyte proliferation, recapitulating sympathetic neuron–deficient hearts. Conversely, increasing sympathetic activity by norepinephrine treatment induced Per1/Per2 and suppressed cardiomyocyte proliferation. We further found that the two clock genes negatively regulate myocyte mitosis entry through the Wee1 kinase pathway. Our findings demonstrate a previously unknown link between cardiac neurons and clock genes in regulation of cardiomyocyte proliferation and heart size and provide mechanistic insights for developing neuromodulation strategies for cardiac regen5eration.
논문정보
- Research article
- 2021년 12월 (BRIC 등록일 2021-12-13)
- 국외 연구진
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