ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
HIF-1α Dependent Wound Healing Angiogenesis In Vivo Can Be Controlled by Site-Specific Lentiviral Magnetic Targeting of SHP-2.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
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- Stem cell therapy: a promising frontier in modern medicine with a comprehensive overview of their biology and potential therapeutic applications in chronic non-healing cutaneous injuries.Inflammopharmacology · 2025Review
- The role of multi-omics in biomarker discovery, diagnosis, prognosis, and therapeutic monitoring of tissue repair and regeneration processes.Journal of orthopaedic translation · 2025Review
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- The role of FGF-21 in promoting diabetic wound healing by modulating high glucose-induced inflammation.Heliyon · 2024Article
- The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering.International journal of molecular sciences · 2023Review
- The Effects of the Levosimendan Metabolites OR-1855 and OR-1896 on Endothelial Pro-Inflammatory Responses.Biomedicines · 2023Article
- The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches.International journal of molecular sciences · 2023Review
- Extracellular vesicles modulate key signalling pathways in refractory wound healing.Burns & trauma · 2023Review
- Potent anti-inflammatory responses: Role of hydrogen in IL-1α dominated early phase systemic inflammation.Frontiers in pharmacology · 2023Article
- Photogenerated reactive oxygen species and hyperthermia by CuJournal of nanobiotechnology · 2022Article
- Cx43 Promotes Endothelial Cell Migration and Angiogenesis via the Tyrosine Phosphatase SHP-2.International journal of molecular sciences · 2021Article
- Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering.Nanomaterials (Basel, Switzerland) · 2021Review
- Review
- Exploring microRNAs in diabetic chronic cutaneous ulcers: Regulatory mechanisms and therapeutic potential.British journal of pharmacology · 2020Review
- Nucleic-Acid Structures as Intracellular Probes for Live Cells.Advanced materials (Deerfield Beach, Fla.) · 2020Review
- SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs.Frontiers in physiology · 2020Article
- The Phosphatase SHP-2 Activates HIF-1α in Wounds In Vivo by Inhibition of 26S Proteasome Activity.International journal of molecular sciences · 2019Article
- Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in Sepsis.EBioMedicine · 2019Article
- Emerging Roles of Redox-Mediated Angiogenesis and Oxidative Stress in Dermatoses.Oxidative medicine and cellular longevity · 2019Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia promotes vascularization by stabilization and activation of the hypoxia inducible factor 1α (HIF-1α), which constitutes a target for angiogenic gene therapy. However, gene therapy is hampered by low gene delivery efficiency and non-specific side effects. Here, we developed a gene transfer technique based on magnetic targeting of magnetic nanoparticle-lentivirus (MNP-LV) complexes allowing site-directed gene delivery to individual wounds in the dorsal skin of mice. Using this technique, we were able to control HIF-1α dependent wound healing angiogenesis in vivo via site-specific modulation of the tyrosine phosphatase activity of SHP-2. We thus uncover a novel physiological role of SHP-2 in protecting HIF-1α from proteasomal degradation via a Src kinase dependent mechanism, resulting in HIF-1α DNA-binding and transcriptional activity in vitro and in vivo. Excitingly, using targeting of MNP-LV complexes, we achieved simultaneous expression of constitutively active as well as inactive SHP-2 mutant proteins in separate wounds in vivo and hereby specifically and locally controlled HIF-1α activity as well as the angiogenic wound healing response in vivo. Therefore, magnetically targeted lentiviral induced modulation of SHP-2 activity may be an attractive approach for controlling patho-physiological conditions relying on hypoxic vessel growth at specific sites.
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