| Role of Neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment |
| Min Hee Park1,2,3,#, Woo-Kie Min4,6,#, Hee Kyung Jin1,5, Jae-sung Bae1,2,3,* |
1Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea,
2Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea,
3Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program,, Kyungpook National University, Daegu, Korea,
4Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea,
5Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea |
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Abstract
The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) function such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction despite of NPY injection. Transforming growth factor-beta (TGF-モ) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in bone marrow. Therefore, this study reveals new role of NPY in bone marrow HSC microenvironment, and provides insight into the therapeutic application of this neuropeptide.
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| Abstract, Accepted Manuscript(in press) [Submitted on November 3, 2015, Accepted on November 3, 2015] |
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