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Published on: October 28, 2019
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Endorepellin evokes autophagy in endothelial cells
Chiara Poluzzi1, Joshua Casulli1, Atul Goyal1
1From the Department of Pathology, Anatomy, and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
The Journal of Biological Chemistry
|April 17, 2014
Summary
Endorepellin, an angiostatic protein fragment, triggers autophagy in endothelial cells by down-regulating VEGFR2. This process involves the tumor suppressor gene Peg3 and enhances anti-angiogenesis strategies.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Endorepellin, a perlecan fragment, inhibits angiogenesis by targeting VEGFR2 and α2β1 integrin.
- Autophagy is a cellular process involved in degradation and recycling of cellular components.
Purpose of the Study:
- To investigate the role of endorepellin in inducing autophagy in endothelial cells.
- To elucidate the molecular mechanisms underlying endorepellin-induced autophagy.
Main Methods:
- Assessed autophagic markers (Beclin 1, LC3, p62) and Peg3 expression.
- Utilized VEGFR2 inhibition (SU5416) and domain-specific endorepellin variants.
- Examined co-localization of Peg3 with autophagosomes.
- Correlated autophagy with capillary morphogenesis inhibition.
Main Results:
- Soluble endorepellin induced autophagy by modulating Beclin 1, LC3, and p62 expression.
- Endorepellin upregulated Peg3 and its co-localization with autophagic markers.
- Autophagy induction was dependent on VEGFR2 downregulation via endorepellin's LG1/2 domains, independent of α2β1 integrin binding.
- VEGFR2 inhibition blocked endorepellin-induced BECN1 promoter activity.
- Endorepellin-induced autophagy correlated with inhibited capillary morphogenesis.
Conclusions:
- Endorepellin induces endothelial cell autophagy via a VEGFR2-dependent, α2β1 integrin-independent pathway.
- Peg3 plays a significant role in endorepellin-mediated autophagy.
- This mechanism offers a novel strategy to enhance the anti-angiogenic effects of endorepellin.
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