2006 Fiscal Year Final Research Report Summary
Role of fibrinolytic factors in the regulation of hematopoiesis
| Project/Area Number |
17591011
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Juntendo University |
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Principal Investigator |
BEATE Heissig Juntendo University, School of Medicine, Assistant Professor, 大学院医学研究科, 講師 (30372931)
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| Project Period (FY) |
2005 – 2006
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| Keywords | plasminogen / plasmin / plasminogen activator / matrix metalloproteinase / G-CSF / angiogenesis / mobilization / differentiation |
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| Research Abstract |
The overall question in the two-year study was to understand how proteases regulate bone marrow(BM)-derived hematopoietic and endothelial cell/stem cell mobilization. We focused on two proteolytic families, the fibrinolytic cascade and the matrix metalloproteinases (MMPs).
The urokinase plasminogen activator receptor (uPAR), a ligand for the serine proteinase urokinase plasminogen activator (uPA) is involved in cell movement and is part of the fibrinolytic cascade. Quantitative analysis of plasma levels of soluble uPAR (suPAR) in patient plasma samples after G-CSF treatment indicated that suPAR plasma levels correlated to leukocyte counts, but not to CD34+ stem cell counts in the peripheral blood. Therefore we concluded that suPAR is not a good marker for stem cell mobilization.
In another study we demonstrated that low-dose irradiation promotes endothelial progenitor cells (EPC)mobilization through MMP-9 mediated release of kit-ligand and VEGF release from mast cells.
We also were able to demonstrate that G-CSF-driven muscle tissue regeneration was partly mediated by the mobilization of BM-derived EPCs and vascular endothelial growth factor (VEGF) released from neutrophils.
In collaboration with the group of Dr. Raffi, we could show that CXCR4+/VEGF-receptor1+ BM-derived hemangiocytes promote cytokine-driven tissue regeneration.
Taken together, proteases play a role in the stem cell mobilization process. They are critical in shedding/releasing extracellular-or membrane-bound growth factors resulting in their bioavailability.
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Research Products
(14 results)
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[Journal Article] Cytokine-mediated deployment of SDF-1 induces revascularisation through recruitment of CXCR4+ hemangiocytes.2006
Author(s)
Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM, Hooper ATA, Amano H, Avecilla ST, Heissig B, Hattori K, Zhang F, Hicklin DJ, Wu Y, Zhu Z, Salari H, Werb Z, Hackett NR, Crystal RG, Lyden D, Raffi S.
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Journal Title
Nat.Med.(Epub)(Erratum) 12(5), 12(8)
Pages: 557-567, 978
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils.2005
Author(s)
Ohki Y, Heissig B, Sato Y, Akiyama H, Zhu Z, Hicklin DJ, Shimada K, Ogawa H, Daida H, Hattori K, Ohsaka A.
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Journal Title
FASEB 19(14)
Pages: 2005-07
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 「研究成果報告書概要(欧文)」より2005
Author(s)
Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T, Zhu Z, Hicklin DJ, Okumura K, Ogawa H, Werb Z, Hattori K.
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Journal Title
J.Exp.Med. 202(6)
Pages: 739-50
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