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Nonproteolytic Properties of Murine Alternatively Spliced Tissue Factor: Implications for Integrin-Mediated Signaling in Murine Models

Overview of attention for article published in Molecular Medicine, April 2012
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Title
Nonproteolytic Properties of Murine Alternatively Spliced Tissue Factor: Implications for Integrin-Mediated Signaling in Murine Models
Published in
Molecular Medicine, April 2012
DOI 10.2119/molmed.2011.00416
Pubmed ID
Authors

Richard C. Godby, Yascha W. van den Berg, Ramprasad Srinivasan, Robert Sturm, David Y. Hui, Stephen F. Konieczny, Bruce J. Aronow, Evgeny Ozhegov, Wolfram Ruf, Henri H. Versteeg, Vladimir Y. Bogdanov

Abstract

This study was performed to determine whether murine alternatively spliced tissue factor (masTF) acts analogously to human alternatively spliced tissue factor (hasTF) in promoting neovascularization via integrin ligation. Immunohistochemical evaluation of a spontaneous murine pancreatic ductal adenocarcinoma model revealed increased levels of masTF and murine full-length tissue factor (mflTF) in tumor lesions compared with benign pancreas; furthermore, masTF colocalized with mflTF in spontaneous aortic plaques of Ldlr(-/-) mice, indicating that masTF is likely involved in atherogenesis and tumorigenesis. Recombinant masTF was used to perform in vitro and ex vivo studies examining its integrin-mediated biologic activity. Murine endothelial cells (ECs) rapidly adhered to masTF in a β3-dependent fashion. Using adult and embryonic murine ECs, masTF potentiated cell migration in transwell assays. Scratch assays were performed using murine and primary human ECs; the effects of masTF and hasTF were comparable in murine ECs, but in human ECs, the effects of hasTF were more pronounced. In aortic sprouting assays, the potency of masTF-triggered vessel growth was undistinguishable from that observed with hasTF. The proangiogenic effects of masTF were found to be Ccl2-mediated, yet independent of vascular endothelial growth factor. In murine ECs, masTF and hasTF upregulated genes involved in inflammatory responses; murine and human ECs stimulated with masTF and hasTF exhibited increased interaction with murine monocytic cells under orbital shear. We propose that masTF is a functional homolog of hasTF, exerting some of its key effects via β3 integrins. Our findings have implications for the development of murine models to examine the interplay between blood coagulation, atherosclerosis and cancer.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 2 8%
Unknown 22 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 25%
Professor 3 13%
Researcher 3 13%
Student > Master 3 13%
Professor > Associate Professor 2 8%
Other 5 21%
Unknown 2 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 38%
Medicine and Dentistry 8 33%
Biochemistry, Genetics and Molecular Biology 4 17%
Nursing and Health Professions 1 4%
Unknown 2 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 April 2012.
All research outputs
#11,396,665
of 12,819,611 outputs
Outputs from Molecular Medicine
#522
of 586 outputs
Outputs of similar age
#102,619
of 119,224 outputs
Outputs of similar age from Molecular Medicine
#19
of 20 outputs
Altmetric has tracked 12,819,611 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 586 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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