Induction and expression of anti-angiogenic vasohibins in the hematopoietic stem/progenitor cell population.
Haematopoiesis and blood vessel formation are closely associated, with several molecules employed by both systems. Recently, vasohibin-1 (VASH1), an endothelium-derived negative feedback regulator of angiogenesis, has been isolated and characterized. VASH1 is induced by VEGF or bFGF in endothelial cells (ECs) and inhibits their proliferation and migration. However, there are no data on the induction and expression of VASH1 in haematopoietic cells (HCs). Here, we show that the haematopoietic stem cell (HSC) population, but not haematopoietic progenitors (HPs) or mature HCs from adult bone marrow (BM) constitutively express VASH1. However, HPs, but not HSCs, can be induced to express VASH1 after BM suppression by 5-FU. Knock-down of the VASH1 gene in VASH1(+) leukaemia cells induced cell proliferation. These results suggest a role for VASH1 in negative feedback regulation of HP proliferation during recovery following BM ablation.
Naito
Hisamichi
H
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Kidoya
Hiroyasu
H
Sato
Yasufumi
Y
Takakura
Nobuyuki
N
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007511:Ischemia; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D018797:Cell Cycle Proteins; C493181:VASH1 protein, human; C510089:Vash1 protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; D005472:Fluorouracil