ArticlePloS one2014
Epidermal or dermal specific knockout of PHD-2 enhances wound healing and minimizes ischemic injury.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- New Pathways for the Skin's Stress Response: The Cholinergic Neuropeptide SLURP-1 Can Activate Mast Cells and Alter Cytokine Production in Mice.Frontiers in immunology · 2021Article
- Impaired Neovascularization in Aging.Advances in wound care · 2020Review
- Early-Life Iron Deficiency Alters Glucose Transporter-1 Expression in the Adult Rodent Hippocampus.The Journal of nutrition · 2019Article
- Epithelial HIF-1α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis.The Journal of clinical investigation · 2019Article
- Acceleration of Diabetic Wound Healing with PHD2- and miR-210-Targeting Oligonucleotides.Tissue engineering. Part A · 2019Article
- PHD-2 Suppression in Mesenchymal Stromal Cells Enhances Wound Healing.Plastic and reconstructive surgery · 2018Article
- Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress.Nutrients · 2017Review
- Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function.Cellular and molecular gastroenterology and hepatology · 2017Review
- New Insights into Protein Hydroxylation and Its Important Role in Human Diseases.Biochimica et biophysica acta · 2016Review
- Local Delivery of PHD2 siRNA from ROS-Degradable Scaffolds to Promote Diabetic Wound Healing.Advanced healthcare materials · 2016Article
- Genetic tools for identifying and manipulating fibroblasts in the mouse.Differentiation; research in biological diversity · 2016Review
- Short Hairpin RNA Silencing of PHD-2 Improves Neovascularization and Functional Outcomes in Diabetic Wounds and Ischemic Limbs.PloS one · 2016Article
- Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration.Regeneration (Oxford, England) · 2015Article
- The mammalian blastema: regeneration at our fingertips.Regeneration (Oxford, England) · 2015Review
- Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges.Hypoxia (Auckland, N.Z.) · 2015Review
- Signaling hypoxia by hypoxia-inducible factor protein hydroxylases: a historical overview and future perspectives.Hypoxia (Auckland, N.Z.) · 2014Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
introductionHypoxia-inducible factor (HIF)-1α, part of the heterodimeric transcription factor that mediates the cellular response to hypoxia, is critical for the expression of multiple angiogenic growth factors, cell motility, and the recruitment of endothelial progenitor cells. Inhibition of the oxygen-dependent negative regulator of HIF-1α, prolyl hydroxylase domain-2 (PHD-2), leads to increased HIF-1α and mimics various cellular and physiological responses to hypoxia. The roles of PHD-2 in the epidermis and dermis have not been clearly defined in wound healing.
methodsEpidermal and dermal specific PHD-2 knockout (KO) mice were developed in a C57BL/6J (wild type) background by crossing homozygous floxed PHD-2 mice with heterozygous K14-Cre mice and heterozygous Col1A2-Cre-ER mice to get homozygous floxed PHD-2/heterozygous K14-Cre and homozygous floxed PHD-2/heterozygous floxed Col1A2-Cre-ER mice, respectively. Ten to twelve-week-old PHD-2 KO and wild type (WT) mice were subjected to wounding and ischemic pedicle flap model. The amount of healing was grossly quantified with ImageJ software. Western blot and qRT-PCR was run on protein and RNA from primary cells cultured in vitro.
resultsqRT-PCR demonstrated a significant decrease of PHD-2 in keratinocytes and fibroblasts derived from tissue specific KO mice relative to control mice (*p<0.05). Western blot analysis showed a significant increase in HIF-1α and VEGF protein levels in PHD-2 KO mice relative to control mice (*p<0.05). PHD-2 KO mice showed significantly accelerated wound closure relative to WT (*p<0.05). When ischemia was analyzed at day nine post-surgery in a flap model, the PHD-2 tissue specific knockout mice showed significantly more viable flaps than WT (*p<0.05).
conclusionsPHD-2 plays a significant role in the rates of wound healing and response to ischemic insult in mice. Further exploration shows PHD-2 KO increases cellular levels of HIF-1α and this increase leads to the transcription of downstream angiogenic factors such as VEGF.
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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.