LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling

Xiaomeng Wang, Sabu Abraham, Jenny A. G. McKenzie, Natasha Jeffs, Matthew Swire, Vineeta B. Tripathi, Ulrich F. O. Luhmann, Clemens A. K. Lange, Zhenhua Zhai, Helen M. Arthur, James W. B. Bainbridge, Stephen E. Moss () and John Greenwood ()
Additional contact information
Xiaomeng Wang: UCL Institute of Ophthalmology
Sabu Abraham: UCL Institute of Ophthalmology
Jenny A. G. McKenzie: UCL Institute of Ophthalmology
Natasha Jeffs: UCL Institute of Ophthalmology
Matthew Swire: UCL Institute of Ophthalmology
Vineeta B. Tripathi: UCL Institute of Ophthalmology
Ulrich F. O. Luhmann: UCL Institute of Ophthalmology
Clemens A. K. Lange: UCL Institute of Ophthalmology
Zhenhua Zhai: Institute of Genetic Medicine, Newcastle University
Helen M. Arthur: Institute of Genetic Medicine, Newcastle University
James W. B. Bainbridge: UCL Institute of Ophthalmology
Stephen E. Moss: UCL Institute of Ophthalmology
John Greenwood: UCL Institute of Ophthalmology

Nature, 2013, vol. 499, issue 7458, 306-311

Abstract: Abstract Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2-glycoprotein 1 (Lrg1), of previously unknown function. We show that in the presence of transforming growth factor-β1 (TGF-β1), LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-β accessory receptor endoglin, which, in the presence of TGF-β1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-β signalling.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature12345 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:499:y:2013:i:7458:d:10.1038_nature12345

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature12345

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().