ArticleCirculation2012
9-cis retinoic acid promotes lymphangiogenesis and enhances lymphatic vessel regeneration: therapeutic implications of 9-cis retinoic acid for secondary lymphedema.
Article in Circulation, 2012. 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 52 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 94 citations in OpenAlex.
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Rescue of conjunctival lymphatics after mitomycin C induced inhibition in rat eyes: An experimental study.Indian journal of ophthalmology · 2026Article
- Exosomes derived from platelet-rich plasma alleviate synovial inflammation by enhancing synovial lymphatic function.Journal of nanobiotechnology · 2025Article
- Review
- Review of treatment strategies after lymphadenectomy: From molecular therapeutics to immediate microsurgical lymphatic reconstruction.Journal of vascular surgery. Venous and lymphatic disorders · 2024Review
- Quantification of Lymphangiogenesis in the Murine Lymphedema Tail Model Using Intravital Microscopy.Lymphatic research and biology · 2024Article
- Review
- Cardiac Lymphatic Insufficiency Leads to Diastolic Dysfunction Via Myocardial Morphologic Change.JACC. Basic to translational science · 2023Article
- Investigation into the genetics of fetal congenital lymphatic anomalies.Prenatal diagnosis · 2023Article
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- Therapeutic Lymphangiogenesis Is a Promising Strategy for Secondary Lymphedema.International journal of molecular sciences · 2023Review
- Breaking a Vicious Circle: Lymphangiogenesis as a New Therapeutic Target in Wound Healing.Biomedicines · 2023Review
- Prolymphangiogenic Effects of 9-Lymphatic research and biology · 2022Article
- Hydrogen Sulfide Attenuates Lymphedema Via the Induction of Lymphangiogenesis Through a PI3K/Akt-Dependent Mechanism.Journal of the American Heart Association · 2022Article
- Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.Circulation research · 2022Article
- Lymphatic Tissue Bioengineering for the Treatment of Postsurgical Lymphedema.Bioengineering (Basel, Switzerland) · 2022Review
- Pharmacological Treatment of Secondary Lymphedema.Frontiers in pharmacology · 2022Review
- Ultrasonication Improves Solid Phase Synthesis of Peptides Specific for Fibroblast Growth Factor Receptor and for the Protein-Protein Interface RANK-TRAF6.Molecules (Basel, Switzerland) · 2021Article
- Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.Nature communications · 2021Article
- Engineering the Lymphatic Network: A Solution to Lymphedema.Advanced healthcare materials · 2021Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction caused by genetic defects, or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swelling often associated with fibrosis and recurrent infections with no available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. METHODS AND
resultsWe report that RAs promote proliferation, migration, and tube formation of cultured lymphatic endothelial cells by activating fibroblast growth factor receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27(Kip1), p57(Kip2), and the aurora kinases through both an Akt-mediated nongenomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals in mouse trachea, Matrigel plug, and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration.
conclusionThese in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients.
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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.