Identification of adiponectin as a novel hemopoietic stem cell growth factor

被引:148
作者
DiMascio, Leah
Voermans, Carlijn
Uqoezwa, Mweia
Duncan, Andrew
Lu, Danhong
Wu, Judy
Sankar, Uma
Reya, Tannishtha
机构
[1] Duke Univ, Ctr Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[2] Duke Univ, Ctr Med, Sarah Stedman Ctr Nutr & Biabet Res, Durham, NC 27710 USA
关键词
D O I
10.4049/jimmunol.178.6.3511
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The hemopoietic microenvironment consists of a diverse repertoire of cells capable of providing signals that influence hemopoietic stem cell function. Although the role of. ostcoblasts and vascular endothelial cells has recently been characterized, the function of the most abundant cell type in the bone marrow, the adipocyte, is less defined. Given the emergence of a growing number of adipokines, it is. possible that these factors may also play a role in regulating hematopoiesis. Here, we investigated the role of adiponectin, a secreted molecule derived from adipocytes, in hemopoietic stem cell (HSC) function. We show that adiponectin is expressed by components of the HSC niche and its' receptors AdipoR1 and AdipoR2 are expressed by HSCs. At a functional level, adiponectin influences HSCs by increasing their proliferation, while retaining the cells in a functionally immature state as determined by in vitro and in vivo assays. We also demonstrate that adiponectin signaling is required for optimal HSC proliferation both in vitro and in long term hemopoietic reconstitution in vivo. Finally we show that adiponectin stimulation activates p38 MAPK, and that: inhibition of this pathway abrogates adiponectin's proliferative effect on HSCs. These studies collectively identify adiponectin as a novel regulator of HSC function and suggest that it acts through a p38 dependent pathway.
引用
收藏
页码:3511 / 3520
页数:10
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