12,13-dihydroxyoctadecenoic acid regulates hematopoietic stem cell and progenitor cell function in zebrafish and mouse
The FASEB Journal(2012)
摘要
The soluble epoxide hydrolase (sEH) is a fatty acid epoxide metabolizing enzyme and its deletion and/or inhibition have been linked with altered cardiovascular homeostasis. Epoxyeicosatrienoic acids, main substrates of the sEH are known to promote angiogenesis. The morpholino (MO) mediated downregulation/inhibition of the sEH in zebrafish results in a defective caudal vein plexus (CVP). Beside the vascular defects a reduced number of hematopoietic stem and progenitor cells (HSPC) could be observed. A screen of fatty acids revealed that the sEH metabolite 12,13‐dihydroxyoctadecenoic acid (12,13‐ DiHOME) was able to rescue these HSPC defects. In a CFU‐S12 assay a reduced number of colonies could be detected in spleens of those mice that received bone marrow cells from sEH−/− mice in comparison to cells derived from wild type mice, whereas 12,13‐ DiHOME was able to rescue these phenotype. Furthermore sEH−/− mice showed less HSPC mobilization after G‐CSF treatment. Summarized, the sEH activity regulates vascular sprouting of the caudal vein plexus in the zebrafish and its product 12,13‐DiHOME influences hematopoietic stem and progenitor cell function in zebrafish and mouse.
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关键词
hematopoietic stem cell,zebrafish,progenitor cell function,acid
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