期刊
NATURE MEDICINE
卷 19, 期 6, 页码 695-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3155
关键词
-
资金
- US National Institutes of Health (NIH) [DK056638, HL069438]
- German Academic Exchange Service (DAAD)
- NIH National Heart, Lung and Blood Institute (NHLBI) [5F30HL099028-02]
- American Society of Hematology-European Hematology Association (ASH-EHA) research exchange award
- Japan Society for the Promotion of Science (JSPS)
- NIH intramural research program, Center for Cancer Research, NCI
Anticancer chemotherapy drugs challenge hematopoietic tissues to regenerate but commonly produce long-term sequelae. Chemotherapy-induced deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes substantial sensory neuropathy. Here we demonstrate that chemotherapy-induced nerve injury in the bone marrow of mice is a crucial lesion impairing hematopoietic regeneration. Using pharmacological and genetic models, we show that the selective loss of adrenergic innervation in the bone marrow alters its regeneration after genotoxic insult. Sympathetic nerves in the marrow promote the survival of constituents of the stem cell niche that initiate recovery. Neuroprotection by deletion of Trp53 in sympathetic neurons or neuroregeneration by administration of 4-methylcatechol or glial-derived neurotrophic factor (GDNF) promotes hematopoietic recovery. These results demonstrate the potential benefit of adrenergic nerve protection for shielding hematopoietic niches from injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据