ArticleStem cells (Dayton, Ohio)2015
Heparanase released from mesenchymal stem cells activates integrin beta1/HIF-2alpha/Flk-1 signaling and promotes endothelial cell migration and angiogenesis.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Enhancing regenerative medicine: the crucial role of stem cell therapy.Frontiers in neuroscience · 2024Review
- Article
- In Search of the Holy Grail: Stem Cell Therapy as a Novel Treatment of Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2023Review
- Role of heparanase in ARDS through autophagy and exosome pathway (review).Frontiers in pharmacology · 2023Review
- Non-enzymatic heparanase enhances gastric tumor proliferation via TFEB-dependent autophagy.Oncogenesis · 2022Article
- Synthesis of Novel Glycolipid Mimetics of Heparan Sulfate and Their Application in Colorectal Cancer Treatment in a Mouse Model.Chemistry, an Asian journal · 2022Article
- Anticancer Effects with Molecular Docking Confirmation of Newly Synthesized Isatin Sulfonamide Molecular Hybrid Derivatives against Hepatic Cancer Cell Lines.Biomedicines · 2022Article
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis.Stem cells (Dayton, Ohio) · 2021Article
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.Nature reviews. Urology · 2019Review
- Heparanase: A Challenging Cancer Drug Target.Frontiers in oncology · 2019Review
- Magnetic Gold Nanoparticle-Labeled Heparanase Monoclonal Antibody and its Subsequent Application for Tumor Magnetic Resonance Imaging.Nanoscale research letters · 2018Article
- The Transcriptome of Human Endometrial Mesenchymal Stem Cells Under TGFβR Inhibition Reveals Improved Potential for Cell-Based Therapies.Frontiers in cell and developmental biology · 2018Article
- Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury.Stem cells international · 2017Article
- MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy.Stem cells (Dayton, Ohio) · 2016Article
- Article
Corrections and comments
- Erratum issuedCorrigendum.2019
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Heparanase plays important roles in tumor angiogenesis. Our previous study demonstrated that hypoxic preconditioning (HPC) enhanced the angiogenic and therapeutic effects of mesenchymal stem cells (MSCs), effects that were paralleled by enhanced heparanase expression. This study was designed to elucidate the role of heparanase in the improved therapeutic properties of HPC-MSCs and to explore underlying mechanisms using an ischemic rat hind limb model. MSCs transfected with heparanase (MSC(hpa) ) or empty vector (MSC(null) ) were delivered by intramuscular injections to ischemic hind limbs. Hind limbs that received MSC(hpa) recovered blood flow more rapidly at 7 days and acquired higher capillary density at 14 days compared with MSC(null) . Conditioned medium from MSC(hpa) increased endothelial cell migration and promoted greater tube formation relative to that from the MSC(null) groups. Vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1) and its downstream signaling pathway (p38MAPK/HSP27) were significantly increased in human umbilical vein endothelial cells (HUVECs) after treatment with MSC(hpa) conditioned medium. Each of these responses was decreased by cocultured with MSC(hpa-KD) conditioned medium. MSC(hpa) conditioned medium activated hypoxia-inducible factor-2α (HIF-2α) and increased in parallel the transcript level of Flk-1 as determined by chromatin immunoprecipitation-PCR and luciferase assays. Analyses of integrin expression revealed an important role for integrin β1 in the regulation of HIF-2α. All angiogenic effects of MSC(hpa) conditioned medium were abolished by knockdown of integrin β1, HIF-2α, and Flk-1 in HUVECs with selective shRNAs. These findings identify heparanse as a key regulator of angiogenesis by MSCs. We propose a novel pathway wherein heparanse sequentially activates integrin β1, HIF-2α, Flk-1, and p38MAPK/HSP27 with corresponding enhancement of angiogenesis.
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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.