Genetic loci that control the angiogenic response to basic response to basic fibroblast growth factor

Rogers, Michael S.; Rohan, Richard M.; Birsner, Amy E.; D’Amato, Robert J.

doi:10.1096/fj.03-1241com

Cited by 38 publications

(29 citation statements)

References 61 publications

(59 reference statements)

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“…In support of such a function, a chromosomal region including the ATX gene had been associated with angiogenic responsiveness to FGF2 [88]. However, an essential role of ATX for vascular development was only revealed through the generation of ATX null mice [18,19].…”

Section: Atx: Enzymatic Activity Via the Catalytic Lysopld Active Sitementioning

confidence: 99%

Autotaxin (ATX): A multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties

Yuelling

Fuss

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Recent studies have established that autotaxin (ATX), also known as phosphodiesterase Iα/autotaxin (PD-Iα/ATX) or (ecto)nucleotide pyrophosphatase/phosphodiesterase 2 [(E)NPP2], represents a multi-functional and multi-modular protein. ATX was initially thought to function exclusively as a phosphodiesterase/pyrophosphatase. However, it has become apparent that this enzymatically active site, which is ultimately responsible for ATX's originally discovered property of tumor cell motility stimulation, mediates the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA). In addition, a separate functionally active domain, here referred to as the Modulator of Oligodendrocyte Remodeling and Focal adhesion Organization (MORFO) domain, was discovered in studies analyzing the role of ATX during the differentiation of myelinating cells of the central nervous system (CNS), namely oligodendrocytes. This novel domain was found to mediate antiadhesive, i.e. matricellular, properties and to promote morphological maturation of oligodendrocytes. In this review, we summarize our current understanding of ATX's structure-function domains and discuss their contribution to the presently known main functional roles of ATX.

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Section: Atx: Enzymatic Activity Via the Catalytic Lysopld Active Sitementioning

confidence: 99%

Autotaxin (ATX): A multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties

Yuelling

Fuss

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…This model has been extensively used to study genetic variations in angiogenic potential (19)(20)(21)(22) and to quantify the effects of pharmacologic agents on angiogenesis (23,24). We found that mice exposed to a single dose of radiation used for bone marrow transplantation exhibited a long-term decrease in capacity to undergo neovascularization and tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Chronic Suppression of Angiogenesis following Radiation Exposure Is Independent of Hematopoietic Reconstitution

Udagawa¹,

Birsner²,

Wood

et al. 2007

Cancer Research

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Radiation can potentially suppress neovascularization by inhibiting the incorporation of hematopoietic precursors as well as damaging mature endothelial cells. The purpose of these studies was to quantify the effect of radiation on angiogenesis and to examine the relationship between bone marrow reconstitution and neovascularization. Immune competent, severe combined immunodeficient, RAG1-deficient, and green fluorescence protein transgenic mice in the C57 genetic background, as well as the highly angiogenic 129S1/ SvlmJ strain of mice, underwent whole-body or localized exposure to radiation. The hematopoietic systems in the irradiated recipients were restored by bone marrow transfer. Hematopoietic reconstitution was assessed by doing complete blood counts. Angiogenesis was induced in the mouse cornea using 80 ng of purified basic fibroblast growth factor, and the neovascular response was quantified using a slit lamp biomicroscope. Following whole-body exposure and bone marrow transplantation, the hematopoietic system was successfully reconstituted over time, but the corneal angiogenic response was permanently and significantly blunted up to 66%. Localized exposure of the eyes to radiation suppressed corneal angiogenesis comparably to whole-body exposure. Whole-body irradiation with ocular shielding induced bone marrow suppression but did not inhibit corneal neovascularization. In mice exposed to radiation before tumor implantation, the reduced local angiogenic response correlated with significantly reduced growth of tumor cells in vivo. These results indicate that bone marrow suppression does not suppress neovascularization in the mouse cornea and that although hematopoietic stem cells can readily reconstitute peripheral blood, they do not restore a local radiationinduced deficit in neovascular response. [Cancer Res 2007; 67(5):2040-5]

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“…For instance, ATX-transfected Ras-transformed NIH 3T3 cells or purified ATX increased angiogenesis in an in vivo Matrigel plug assay (30). Furthermore, VEGF increases expression of ATX (18,34); ATX was identified as one of the genes that control the angiogenic response to basic fibroblast growth factor (bFGF) (36). Finally, ATX-deficient mice die during embryogenesis and display a vascular defect (41,48).…”

mentioning

confidence: 99%

Phospholipase Cγ Activation Drives Increased Production of Autotaxin in Endothelial Cells and Lysophosphatidic Acid-Dependent Regression

Motiejūnaitė

Aranda

et al. 2010

Molecular and Cellular Biology

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We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase C␥1 (PLC␥) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism by which PLC␥ promoted regression of tubes and blood vessels. Namely, it increased the level of autotaxin (ATX), which is a secreted form of lysophospholipase D that produces lysophosphatidic acid (LPA). LPA promoted motility of endothelial cells, leading to disorganization/regression of tubes in vitro. Furthermore, mice that under-or overexpressed members of this intrinsic destabilization pathway showed either delayed or accelerated, respectively, regression of blood vessels. We conclude that endothelial cells can be instructed to engage a PLC␥-dependent intrinsic destabilization pathway that results in the production of soluble regression factors such as ATX and LPA. These findings are likely to potentiate ongoing efforts to prevent, manage, and eradicate numerous angiogenesis-based diseases such as proliferative diabetic retinopathy and solid tumors.

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Genetic loci that control the angiogenic response to basic response to basic fibroblast growth factor

Cited by 38 publications

References 61 publications

Autotaxin (ATX): A multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties

Autotaxin (ATX): A multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties

Chronic Suppression of Angiogenesis following Radiation Exposure Is Independent of Hematopoietic Reconstitution

Phospholipase Cγ Activation Drives Increased Production of Autotaxin in Endothelial Cells and Lysophosphatidic Acid-Dependent Regression

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