ArticleThe Journal of biological chemistry2014
Endorepellin evokes autophagy in endothelial cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Heparan Sulfate Proteoglycans: Master Regulators of Cellular Signaling, Tissue Development, and Neural Function.Journal of neuroscience research · 2026Review
- Proteoglycans are protagonists in autophagy, lymphangiogenesis, and neurodegenerative diseases.Trends in cell biology · 2026Review
- Targeting autophagy in dysfunctional tumor vasculature.iScience · 2025Review
- Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.International journal of biological sciences · 2025Review
- HOXD9 regulated mitophagy to promote endothelial progenitor cells angiogenesis and deep vein thrombosis recanalization and resolution.Molecular medicine (Cambridge, Mass.) · 2024Article
- Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.International journal of molecular sciences · 2024Article
- Conditional expression of endorepellin in the tumor vasculature attenuates breast cancer growth, angiogenesis and hyaluronan deposition.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Decorin evokes reversible mitochondrial depolarization in carcinoma and vascular endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Proteoglycans in Cancer: Friends or Enemies? A Special Focus on Hepatocellular Carcinoma.Cancers · 2022Review
- The Role of Decorin Proteoglycan in Mitophagy.Cancers · 2022Review
- Mechanoautophagy: Synergies Between Autophagy and Cell Mechanotransduction at Adhesive Complexes.Frontiers in cell and developmental biology · 2022Review
- Extracellular matrix guidance of autophagy: a mechanism regulating cancer growth.Open biology · 2022Review
- A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- ECM-regulation of autophagy: The yin and the yang of autophagy during wound healing.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Research Progress on the Mechanism of Mitochondrial Autophagy in Cerebral Stroke.Frontiers in aging neuroscience · 2021Review
- Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology.The Journal of biological chemistry · 2020Review
- Adaptive response of resistant cancer cells to chemotherapy.Cancer biology & medicine · 2020Review
- Proteoglycan-driven Autophagy: A Nutrient-independent Mechanism to Control Intracellular Catabolism.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, possesses angiostatic activity via dual receptor antagonism, through concurrent binding to the α2β1 integrin and vascular endothelial growth factor receptor 2 (VEGFR2). Here, we discovered that soluble endorepellin induced autophagy in endothelial cells by modulating the expression of Beclin 1, LC3, and p62, three established autophagic markers. Moreover, endorepellin evoked expression of the imprinted tumor suppressor gene Peg3 and its co-localization with Beclin 1 and LC3 in autophagosomes, suggesting a major role for this gene in endothelial cell autophagy. Mechanistically, endorepellin induced autophagy by down-regulating VEGFR2 via the two LG1/2 domains, whereas the C-terminal LG3 domain, the portion responsible for binding the α2β1 integrin, was ineffective. Endorepellin also induced transcriptional activity of the BECN1 promoter in endothelial cells, and the VEGFR2-specific tyrosine kinase inhibitor, SU5416, blocked this effect. Finally, we found a correlation between endorepellin-evoked inhibition of capillary morphogenesis and enhanced autophagy. Thus, we have identified a new role for this endogenous angiostatic fragment in inducing autophagy through a VEGFR2-dependent but α2β1 integrin-independent pathway. This novel mechanism specifically targets endothelial cells and could represent a promising new strategy to potentiate the angiostatic effect of endorepellin and perhaps other angiostatic matrix proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.