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07:49
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling
Xiaomeng Wang1, Sabu Abraham1, Jenny A G McKenzie1
1Department of Cell Biology, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Nature
|July 23, 2013
Summary
Leucine-rich alpha-2-glycoprotein 1 (Lrg1) promotes pathological angiogenesis by interacting with transforming growth factor-β1 (TGF-β1). Inhibiting Lrg1 significantly reduces ocular angiogenesis, revealing it as a novel therapeutic target.
Area of Science:
- Molecular Biology
- Ophthalmology
- Cardiovascular Biology
Background:
- Aberrant neovascularization underlies severe diseases like cancer, blindness, and atherosclerosis.
- Pathological angiogenesis results from dysregulated angiogenic signaling, yet key regulators remain unidentified.
- Understanding these regulators is crucial for developing effective disease treatments.
Purpose of the Study:
- To identify novel regulators of pathological angiogenesis in retinal microvessels.
- To investigate the function and mechanism of the upregulated gene leucine-rich alpha-2-glycoprotein 1 (Lrg1).
Main Methods:
- Transcriptome analysis of retinal microvessels from mouse models of retinal disease.
- In vitro assays to assess the mitogenic effects of LRG1 on endothelial cells.
- In vivo studies using Lrg1 knockout mice and LRG1 antibody blockade.
- Analysis of LRG1 interaction with transforming growth factor-β1 (TGF-β1) and downstream signaling pathways.
Main Results:
- Leucine-rich alpha-2-glycoprotein 1 (Lrg1) was identified as an upregulated gene in pathological retinal neovascularization.
- LRG1, in conjunction with TGF-β1, promotes endothelial cell proliferation and angiogenesis.
- Lrg1 deficiency reduced pathological ocular angiogenesis, and LRG1 blockade attenuated angiogenesis.
- LRG1 directly binds to endoglin, modulating TGF-β1 signaling towards the pro-angiogenic Smad1/5/8 pathway.
Conclusions:
- Leucine-rich alpha-2-glycoprotein 1 (Lrg1) is a novel and significant regulator of angiogenesis.
- LRG1 mediates its pro-angiogenic effects by interacting with the TGF-β signaling pathway.
- Targeting LRG1 offers a potential therapeutic strategy for diseases characterized by pathological angiogenesis.
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