ArticleDiabetes2022
Endothelial Phospholipase Cγ2 Improves Outcomes of Diabetic Ischemic Limb Rescue Following VEGF Therapy.
Article in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 18 citations in OpenAlex.
- Reimagining VEGF Therapy: The Role of PLCγ2 in Pan-Organ Endothelial Networks.Advances in wound care · 2026Article
- Endothelial dysfunction in human diabetic vascular complications: translating single-cell transcriptomics into therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- Diabetic Wound Vasculopathy and Neuropathy: Spotlight on Wound Lipid Signaling.Advances in wound care · 2026Review
- Identification of Skin Multicellular Reprogramming Factors as Potential Treatment for Nonhealing Diabetic Foot Ulcers.Advances in wound care · 2026Article
- Identification of Renal Transcripts Associated with Kidney Function and Prognosis in ANCA-Associated Vasculitis.Journal of the American Society of Nephrology : JASN · 2026Article
- Comprehensive Transcriptomic and Proteomic Analysis of Severe Pressure Ulcer Patients Identifies Molecular Signatures Associated with Impaired T Cell Function.Biomolecules · 2025Article
- Direct in vivo reprogramming to relieve tissue ischemia via induced vasculogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Exosomes derived from human amniotic mesenchymal stem cells promotes angiogenesis in hUVECs by delivering novel miRNA N-194.Molecular medicine (Cambridge, Mass.) · 2025Article
- Tissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing rescues perfusion and diabetic ischemic wound healing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Enhancing VEGF therapy in T2D wounds with PLCγ2 epigenetic targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Mission SpaceX CRS-16 RRRM-1 space flight induced skin genomic plasticity via an epigenetic trigger.iScience · 2024Article
- STimage-1K4M: A histopathology image-gene expression dataset for spatial transcriptomics.Advances in neural information processing systems · 2024Article
- Vasculogenic skin reprogramming requires TET-mediated gene demethylation in fibroblasts for rescuing impaired perfusion in diabetes.Nature communications · 2024Article
- Impact of Epigenetics, Diet, and Nutrition-Related Pathologies on Wound Healing.International journal of molecular sciences · 2024Review
- Collagenase-based wound debridement agent induces extracellular matrix supporting phenotype in macrophages.Scientific reports · 2024Article
- Tissue Nanotransfection Silicon Chip and Related Electroporation-Based Technologies for In Vivo Tissue Reprogramming.Nanomaterials (Basel, Switzerland) · 2024Review
- Rescue of murine hind limb ischemia via angiogenesis and lymphangiogenesis promoted by cellular communication network factor 2.Scientific reports · 2023Article
- Human fetal dermal fibroblast-myeloid cell diversity is characterized by dominance of pro-healing Annexin1-FPR1 signaling.iScience · 2023Article
- Tissue nanotransfection causes tumor regression by its effect on nanovesicle cargo that alters microenvironmental macrophage state.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Therapeutic vascular endothelial growth factor (VEGF) replenishment has met with limited success for the management of critical limb-threatening ischemia. To improve outcomes of VEGF therapy, we applied single-cell RNA sequencing (scRNA-seq) technology to study the endothelial cells of the human diabetic skin. Single-cell suspensions were generated from the human skin followed by cDNA preparation using the Chromium Next GEM Single-cell 3' Kit v3.1. Using appropriate quality control measures, 36,487 cells were chosen for downstream analysis. scRNA-seq studies identified that although VEGF signaling was not significantly altered in diabetic versus nondiabetic skin, phospholipase Cγ2 (PLCγ2) was downregulated. The significance of PLCγ2 in VEGF-mediated increase in endothelial cell metabolism and function was assessed in cultured human microvascular endothelial cells. In these cells, VEGF enhanced mitochondrial function, as indicated by elevation in oxygen consumption rate and extracellular acidification rate. The VEGF-dependent increase in cell metabolism was blunted in response to PLCγ2 inhibition. Follow-up rescue studies therefore focused on understanding the significance of VEGF therapy in presence or absence of endothelial PLCγ2 in type 1 (streptozotocin-injected) and type 2 (db/db) diabetic ischemic tissue. Nonviral topical tissue nanotransfection technology (TNT) delivery of CDH5 promoter-driven PLCγ2 open reading frame promoted the rescue of hindlimb ischemia in diabetic mice. Improvement of blood flow was also associated with higher abundance of VWF+/CD31+ and VWF+/SMA+ immunohistochemical staining. TNT-based gene delivery was not associated with tissue edema, a commonly noted complication associated with proangiogenic gene therapies. Taken together, our study demonstrates that TNT-mediated delivery of endothelial PLCγ2, as part of combination gene therapy, is effective in diabetic ischemic limb rescue.
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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.