期刊
EMBO JOURNAL
卷 34, 期 12, 页码 1648-1660出版社
WILEY-BLACKWELL
DOI: 10.15252/embj.201490174
关键词
bone marrow microenvironment; hematopoietic stem cell; neuropeptide Y; regeneration; sympathetic nervous system
资金
- Bio & Medical Technology Development Program [2012M3A9C6049913]
- Basic Science Research Program of the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning, Republic of Korea [2014R1A2A1A10051107]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1636]
- National Research Foundation of Korea [2014R1A2A1A10051107] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY-deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy-induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.
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