title: PPARα regulates endothelial progenitor cell maturation and myeloid lineage differentiation through a NADPH oxidase-dependent mechanism in mice.
abstract: 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.
authors.affiliation: INSERM U1063, Stress Oxydant et Pathologies Métaboliques, Institut de Biologie en Santé Université d'Angers, Angers, France; Department of Biosciences, Biotechnologies and Biofarmaceutic, University of Bari, Bari, Italy; Centre Hospitalo-Universitaire d'Angers, Angers, France.
authors.forename: Luisa
authors.initials: L
authors.lastname: Vergori
authors.forename: Emilie
authors.initials: E
authors.lastname: Lauret
authors.forename: Abderahim
authors.initials: A
authors.lastname: Gaceb
authors.forename: Céline
authors.initials: C
authors.lastname: Beauvillain
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Martinez
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000502:physiology*; D047493:PPAR alpha / Q000502:physiology*
chemical_list: D047493:PPAR alpha; D019255:NADPH Oxidases
keywords: Bone marrow; Differentiation; Endothelial cell; Hematopoietic progenitors