ArticlePloS one2016
Signaling of Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- VEGFR2 is required for VEGF-C-VEGFR3-PI3Kα-mediated sprouting lymphangiogenesis.Nature communications · 2026Article
- The Functional Study of Prostaglandin EChonnam medical journal · 2026Article
- Endothelial system dysregulation underlies keloid development and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Inhibition of Th2 Differentiation Accelerates Chronic Wound Healing by Facilitating Lymphangiogenesis.Biomedicines · 2025Article
- Investigating the role of the mPGES-PGE₂-EP4 pathway inFrontiers in veterinary science · 2025Article
- Cellular and molecular mechanisms of skin wound healing.Nature reviews. Molecular cell biology · 2024Review
- Two transcriptionally and functionally distinct waves of neutrophils during mouse acute liver injury.Hepatology communications · 2024Article
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Ontogenesis of the Mouse Ocular Surface Lymphatic Vascular Network.Investigative ophthalmology & visual science · 2023Article
- Thromboxane prostanoid signaling in macrophages attenuates lymphedema and facilitates lymphangiogenesis in mice : TP signaling and lymphangiogenesis.Molecular biology reports · 2023Article
- Inhibition of TP signaling promotes endometriosis growth and neovascularization.Molecular medicine reports · 2023Article
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation.The Journal of experimental medicine · 2023Article
- Alloantigen-activated (AAA) CD4Journal of experimental & clinical cancer research : CR · 2021Article
- The complex role of prostaglandin EAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2021Review
- Review
- The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming.Frontiers in immunology · 2021Review
- Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma.Frontiers in oncology · 2021Review
- RAMP1 signaling in immune cells regulates inflammation-associated lymphangiogenesis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Role of the PGE2 receptor in ischemia-reperfusion injury of the rat retina.Molecular vision · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymphangiogenesis plays an important role in homeostasis, metabolism, and immunity, and also occurs during wound-healing. Here, we examined the roles of prostaglandin E2 (PGE2) receptor (EP) signaling in enhancement of lymphangiogenesis in wound healing processes. The hole-punch was made in the ears of male C57BL/6 mice using a metal ear punch. Healing process and lymphangiogenesis together with macrophage recruitment were analyzed in EP knockout mice. Lymphangiogenesis was up-regulated in the granulation tissues at the margins of punched-hole wounds in mouse ears, and this increase was accompanied by increased expression levels of COX-2 and microsomal prostaglandin E synthase-1. Administration of celecoxib, a COX-2 inhibitor, suppressed lymphangiogenesis in the granulation tissues and reduced the induction of the pro-lymphangiogenic factors, vascular endothelial growth factor (VEGF) -C and VEGF-D. Topical applications of selective EP receptor agonists enhanced the expressions of lymphatic vessel endothelial hyaluronan receptor-1 and VEGF receptor-3. The wound-healing processes and recruitment of CD11b-positive macrophages, which produced VEGF-C and VEGF-D, were suppressed under COX-2 inhibition. Mice lacking either EP3 or EP4 exhibited reduced wound-healing, lymphangiogenesis and recruitment of M2 macrophages, compared with wild type mice. Proliferation of cultured human lymphatic endothelial cells was not detected under PGE2 stimulation. Lymphangiogenesis and recruitment of M2 macrophages that produced VEGF-C/D were suppressed in mice treated with a COX-2 inhibitor or lacking either EP3 or EP4 during wound healing. COX-2 and EP3/EP4 signaling may be novel targets to control lymphangiogenesis in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.