PPARα Regulates Endothelial Progenitor Cell Maturation and Myeloid Lineage Differentiation Through a NADPH Oxidase‐Dependent Mechanism in Mice

Peroxisome proliferator‐activated receptor‐alpha (PPARα) is a key modulator of lipid metabolism. Here, we propose that PPARα regulates the maturation and function of bone marrow (BM) progenitor cells. Although PPARα deletion increased the number of BM‐resident cells and the differentiation of endoth...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2015-04, Vol.33 (4), p.1292-1303
Main Authors: Vergori, Luisa, Lauret, Emilie, Gaceb, Abderahim, Beauvillain, Céline, Andriantsitohaina, Ramaroson, Martinez, M. Carmen
Format: Article
Language:English
Subjects:
Animals
Bone marrow
Cell Differentiation - physiology
Cell Lineage - physiology
Cell Movement - physiology
Cells, Cultured
Differentiation
Endothelial cell
Endothelial Progenitor Cells - physiology
Hematopoietic progenitors
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NADPH Oxidases - physiology
PPAR alpha - physiology
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Summary:Peroxisome proliferator‐activated receptor‐alpha (PPARα) is a key modulator of lipid metabolism. Here, we propose that PPARα regulates the maturation and function of bone marrow (BM) progenitor cells. Although PPARα deletion increased the number of BM‐resident cells and the differentiation of endothelial progenitor cells (EPCs) and monocytic progenitor cells, it impaired re‐endothelialization of injured carotid artery that was associated with reduced circulating EPCs. Also, PPARα deletion diminished the in vivo proangiogenic effect of PPARα agonist without affecting EPC differentiation markers. Macrophage colony‐stimulating factor treatment increased the population of monocytic progenitor cells as well as secretome of BM‐derived cells in PPARα wild‐type but not in knockout mice. In addition, PPARα‐null mice displayed reduced lymphocytes and increased monocytes and neutrophils in the blood. Furthermore, PPARα‐null mice exhibited increments in the number of total cells (as well as of phenotypically distinct subpopulations of lymph node cells) but also a significant alteration in the number of various subpopulations of splenocytes and thymocytes. Finally, PPARα negatively regulated reactive oxygen species derived by NADPH oxidase in BM‐resident progenitor cells. Taken together, our data provide evidence that PPARα is a critical regulator of recruitment, homing, and maturation of BM‐derived progenitor cells. Stem Cells 2015;33:1292–1303
ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1002/stem.1924