ArticlePloS one2016
Activation of Dll4/Notch Signaling and Hypoxia-Inducible Factor-1 Alpha Facilitates Lymphangiogenesis in Lacrimal Glands in Dry Eye.
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 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Corneal lymphangiogenesis as a potential target in dry eye disease - a systematic review.Survey of ophthalmologyPooled it
- Ocular Lymphatics in Health and Disease.Diagnostics (Basel, Switzerland) · 2026Review
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Pathophysiological Insights Into the Role of Osteoclasts in Osteoarthritis: Mechanisms, Therapeutic Targets, and Future Directions.Journal of inflammation research · 2025Review
- New targets of nascent lymphatic vessels in ocular diseases.Frontiers in physiology · 2024Review
- Inhibition of Hepatic Stellate Cell Activation Suppresses Tumorigenicity of Hepatocellular Carcinoma in Mice.The American journal of pathology · 2021Article
- Corneal Lymphangiogenesis: Current Pathophysiological Understandings and Its Functional Role in Ocular Surface Disease.International journal of molecular sciences · 2021Review
- Implications for preeclampsia: hypoxia-induced Notch promotes trophoblast migration.Reproduction (Cambridge, England) · 2021Article
- Impact of Air Pollution and Weather on Dry Eye.Journal of clinical medicine · 2020Review
- Preserved Corneal Lamellar Grafting Reduces Inflammation and Promotes Wound Healing in a Scleral Defect Rabbit Model.Translational vision science & technology · 2020Article
- PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland.International journal of ophthalmology · 2020Article
- Dry Eye Management: Targeting the Ocular Surface Microenvironment.International journal of molecular sciences · 2017Review
- Notch: A multi-functional integrating system of microenvironmental signals.Developmental biology · 2016Review
- Notch2 Signaling Regulates the Proliferation of Murine Bone Marrow-Derived Mesenchymal Stem/Stromal Cells via c-Myc Expression.PloS one · 2016Article
- Orbital lymphatic vessels: immunohistochemical detection in the lacrimal gland, optic nerve, fat tissue, and extrinsic oculomotor muscles.Arquivos brasileiros de oftalmologiaArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeBy using hypoxia-inducible factor-1 alpha conditional knockout (HIF-1α CKO) mice and a dry eye (DE) mouse model, we aimed to determine the role played by delta-like ligand 4 (Dll4)/Notch signaling and HIF-1α in the lymphangiogenesis of lacrimal glands (LGs).
methodsC57BL/6 mice were housed in a controlled-environment chamber for DE induction. During DE induction, the expression level of Dll4/Notch signaling and lymphangiogenesis in LGs was measured by quantitative RT-PCR, immunoblot, and immunofluorescence staining. Next, lymphangiogenesis was measured after Dll4/Notch signal inhibition by anti-Dll4 antibody or γ-secretase inhibitor. Using HIF-1α CKO mice, the expression of Dll4/Notch signaling and lymphangiogenesis in LGs of DE-induced HIF-1α CKO mice were assessed. Additionally, the infiltration of CD45+ cells in LGs was assessed by immunohistochemical (IHC) staining and flow cytometry for each condition.
resultsDE significantly upregulated Dll4/Notch and lymphangiogenesis in LGs. Inhibition of Dll4/Notch significantly suppressed lymphangiogenesis in LGs. Compared to wild-type (WT) mice, DE induced HIF-1α CKO mice showed markedly low levels of Dll4/Notch and lymphangiogenesis. Inhibition of lymphangiogenesis by Dll4/Notch suppression resulted in increased CD45+ cell infiltration in LGs. Likewise, CD45+ cells infiltrated more in the LGs of HIF-1α CKO DE mice than in non-DE HIF-1α CKO mice.
conclusionsDll4/Notch signaling and HIF-1α are closely related to lymphangiogenesis in DE-induced LGs. Lymphangiogenesis stimulated by Dll4/Notch and HIF-1α may play a role in protecting LGs from DE-induced inflammation by aiding the clearance of immune cells from LGs.
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