TY - JOUR
T1 - Loss of myeloid cell-derived vascular endothelial growth factor accelerates fibrosis
AU - Stockmann, Christian
AU - Kerdiles, Yann
AU - Nomaksteinsky, Marc
AU - Weidemann, Alexander
AU - Takeda, Norihiko
AU - Doedens, Andrew
AU - Torres-Collado, Antonio X.
AU - Iruela-Arispe, Luisa
AU - Nizet, Victor
AU - Johnson, Randall S.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/3/2
Y1 - 2010/3/2
N2 - Tissue injury initiates a complex series of events that act to restore structure and physiological homeostasis. Infiltration of inflammatory cells and vascular remodeling are both keystones of this process. However, the role of inflammation and angiogenesis in general and, more specifically, the significance of inflammatory cell-derived VEGF in this context are unclear. To determine the role of inflammatory cell-derived VEGF in a clinically relevant and chronically inflamed injury, pulmonary fibrosis, we deleted the VEGF-A gene in myeloid cells. In a model of pulmonary fibrosis in mice, deletion of VEGF in myeloid cells resulted in significantly reduced formation of blood vessels; however, it causes aggravated fibrotic tissue damage. This was accompanied by a pronounced decrease in epithelial cell survival and a striking increase inmyofibroblast invasion. The drastic increase in fibrosis following loss of myeloid VEGF in the damaged lungswas also marked by increased levels of hypoxia-inducible factor (HIF) expression and Wnt/β-catenin signaling. This demonstrates that the process of angiogenesis, driven by myeloid cell-derived VEGF, is essential for the prevention of fibrotic damage.
AB - Tissue injury initiates a complex series of events that act to restore structure and physiological homeostasis. Infiltration of inflammatory cells and vascular remodeling are both keystones of this process. However, the role of inflammation and angiogenesis in general and, more specifically, the significance of inflammatory cell-derived VEGF in this context are unclear. To determine the role of inflammatory cell-derived VEGF in a clinically relevant and chronically inflamed injury, pulmonary fibrosis, we deleted the VEGF-A gene in myeloid cells. In a model of pulmonary fibrosis in mice, deletion of VEGF in myeloid cells resulted in significantly reduced formation of blood vessels; however, it causes aggravated fibrotic tissue damage. This was accompanied by a pronounced decrease in epithelial cell survival and a striking increase inmyofibroblast invasion. The drastic increase in fibrosis following loss of myeloid VEGF in the damaged lungswas also marked by increased levels of hypoxia-inducible factor (HIF) expression and Wnt/β-catenin signaling. This demonstrates that the process of angiogenesis, driven by myeloid cell-derived VEGF, is essential for the prevention of fibrotic damage.
KW - Angiogenesis
KW - Fibrosis
KW - Hypoxia
KW - Inflammation
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U2 - 10.1073/pnas.0912766107
DO - 10.1073/pnas.0912766107
M3 - Article
C2 - 20142499
AN - SCOPUS:77749254869
VL - 107
SP - 4329
EP - 4334
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 9
ER -