NDLI: Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols

Content Provider	PubMed Central
Author	Timo, Frömel Jungblut, Benno Hu, Jiong Caroline, Trouvain Eduardo, Barbosa-sicard Popp, Rüdiger Stefan, Liebner Dimmeler, Stefanie Hammock, Bruce D. Fleming, Ingrid
Abstract	Fatty acid epoxides are important lipid signaling molecules involved in the regulation of vascular tone and homeostasis. Tissue and plasma levels of these mediators are determined by the activity of cytochrome P450 epoxygenases and the soluble epoxide hydrolase (sEH), and targeting the latter is an effective way of manipulating epoxide levels in vivo. We investigated the role of the sEH in regulating the mobilization and proliferation of progenitor cells with vasculogenic/reparative potential. Our studies revealed that sEH down-regulation/inhibition impaired the development of the caudal vein plexus in zebrafish, and decreased the numbers of lmo2/cmyb-positive progenitor cells therein. In mice sEH inactivation attenuated progenitor cell proliferation (spleen colony formation), but the sEH products 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME) and 11,12- dihydroxyeicosatrienoic acid stimulated canonical Wnt signaling and rescued the effects of sEH inhibition. In murine bone marrow, the epoxide/diol content increased during G-CSF–induced progenitor cell expansion and mobilization, and both mobilization and spleen colony formation were reduced in sEH−/− mice. Similarly, sEH−/− mice showed impaired functional recovery following hindlimb ischemia, which was rescued following either the restoration of bone marrow sEH activity or treatment with 12,13-DiHOME. Thus, sEH activity is required for optimal progenitor cell proliferation, whereas long-term sEH inhibition is detrimental to progenitor cell proliferation, mobilization, and vascular repair.
Related Links	http://dx.doi.org/10.1073/pnas.1206493109
Starting Page	9995
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	25
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-06-19
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols.

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Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols

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