Related Experiment Video
Updated: Jun 1, 2026
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Myoferlin gene silencing decreases Tie-2 expression in vitro and angiogenesis in vivo
Carol Yu1, Arpeeta Sharma, Andy Trane
1The Providence Heart and Lung Institute, The James Hogg Research Centre, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Angiogenesis consists in the growth of new blood vessels from pre-existing ones. Although anti-angiogenesis interventions have been shown to have therapeutic properties in human diseases such as cancer, their effect is only partial and the identification of novel modulators of angiogenesis is warranted. Recently, we reported the unexpected proteomic identification in endothelial cells (EC) of Myoferlin, a member of the Ferlin family of transmembrane proteins. Ferlins are well known to regulate the fusion of lipid vesicles at the plasma membrane in muscle cells, and we showed that Myoferlin gene knockdown not only decreases lipid vesicle fusion in EC but also attenuates Vascular Endothelial Growth Factor (VEGF) Receptor-2 (VEGFR-2) expression. Herein, we show that Myoferlin gene silencing in cultured EC also results in attenuated expression of a second tyrosine kinase receptor, Tie-2, which is another well-described angiogenic receptor. Most importantly, we provide evidence that delivery of a low-volume Myoferlin siRNA preparation in mouse tissues results in attenuated angiogenesis and edema formation. This provides the first evidence that acute Myoferlin knockdown has anti-angiogenic effects and validates Myoferlin as an anti-angiogenesis target. Furthermore, this supports the unexpected but increasingly accepted concept that proper tyrosine kinase receptors expression at the plasma membrane requires Myoferlin.
Insights
Myoferlin knockdown in endothelial cells reduces expression of key angiogenic receptors, demonstrating its role in new blood vessel growth. Acute Myoferlin silencing in mice effectively inhibits angiogenesis and edema, validating it as a therapeutic target.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Angiogenesis, the formation of new blood vessels, is crucial in diseases like cancer, but current anti-angiogenesis therapies are only partially effective.
- Identifying novel modulators of angiogenesis is essential for developing improved therapeutic strategies.
- Myoferlin, a transmembrane protein, was recently identified in endothelial cells and implicated in lipid vesicle fusion and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) expression.
Purpose of the Study:
- To investigate the role of Myoferlin in regulating angiogenic receptors beyond VEGFR-2.
- To determine if acute Myoferlin knockdown exhibits anti-angiogenic effects in vivo.
- To validate Myoferlin as a potential therapeutic target for anti-angiogenesis strategies.
Main Methods:
- Gene silencing of Myoferlin in cultured endothelial cells (EC).
- Assessment of tyrosine kinase receptor expression (VEGFR-2 and Tie-2) following Myoferlin knockdown.
- In vivo delivery of Myoferlin siRNA in mouse tissues to evaluate effects on angiogenesis and edema formation.
Main Results:
- Myoferlin gene silencing in EC led to decreased expression of both VEGFR-2 and Tie-2, key receptors involved in angiogenesis.
- Acute knockdown of Myoferlin in mouse tissues using siRNA resulted in significant attenuation of angiogenesis.
- Myoferlin silencing also reduced edema formation in mouse tissues, suggesting a role in vascular permeability.
Conclusions:
- Myoferlin plays a critical role in maintaining the expression of essential angiogenic receptors, including Tie-2, at the plasma membrane of endothelial cells.
- Acute Myoferlin knockdown demonstrates significant anti-angiogenic effects in vivo, validating Myoferlin as a novel therapeutic target.
- These findings support the concept that Myoferlin is essential for proper tyrosine kinase receptor expression and function in angiogenesis.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:10Mechanism of Angiogenesis
01:16TGF - β Signaling Pathway