title: Hypoxia-induced proliferation of tissue-resident endothelial progenitor cells in the lung.
abstract: Exposure to hypoxia induces changes in the structure and functional phenotypes of the cells composing the pulmonary vascular wall from larger to most peripheral vessels. Endothelial progenitor cells (EPCs) may be involved in vascular endothelial repair. Resident EPCs with a high proliferative potential are found in the pulmonary microcirculation. However, their potential location, identification, and functional role have not been clearly established. We investigated whether resident EPCs or bone marrow (BM)-derived EPCs play a major role in hypoxic response of pulmonary vascular endothelial cells (PVECs). Mice were exposed to hypoxia. The number of PVECs transiently decreased followed by an increase in hypoxic animals. Under hypoxic conditions for 1 wk, prominent bromodeoxyuridine incorporation was detected in PVECs. Some Ki67-positive cells were detected among PVECs after 1 wk under hypoxic conditions, especially in the capillaries. To clarify the origin of proliferating endothelial cells, we used BM chimeric mice expressing green fluorescent protein (GFP). The percentage of GFP-positive PVECs was low and constant during hypoxia in BM-transplanted mice, suggesting little engraftment of BM-derived cells in lungs under hypoxia. Proliferating PVECs in hypoxic animals showed increased expression of CD34, suggesting hypoxia-induced gene expression and cell surface antigen of EPC or stem/progenitor cells markers. Isolated PVECs from hypoxic mice showed colony- and tube-forming capacity. The present study indicated that hypoxia could induce proliferation of PVECs, and the origin of these cells might be tissue-resident EPCs.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan rintaro09281980@yahoo.co.jp.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Nishimura
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Nishiwaki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Suda
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Urushibara
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Takayanagi
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Terada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Sakao
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D016026:Bone Marrow Transplantation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D008168:Lung / Q000098:blood supply / Q000166:cytology; D008297:Male; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: EPCs; endothelial cells; hypoxia; proliferation