Neuropilin-2 contributes to LPS-induced corneal inflammatory lymphangiogenesis

Autor: Ping Liu, Haitao Du, Jun-feng Sun, Fengmin Zhang, Xianling Tang, Liyuan Wang, Du Lingling, Jieying Mai
Rok vydání: 2016
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
government.form_of_government
Genetic Vectors
Enzyme-Linked Immunosorbent Assay
Biology
Corneal inflammation
Adenoviridae
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Cell Movement
medicine
Animals
Corneal Neovascularization
Gene Silencing
Lymphangiogenesis
Fluorescent Antibody Technique
Indirect
Cell Proliferation
Lymphatic Vessels
Keratitis
Mice
Inbred BALB C
Gene knockdown
Macrophages
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-3
medicine.disease
Coculture Techniques
Sensory Systems
Neuropilin-2
Endothelial stem cell
Vascular endothelial growth factor
Disease Models
Animal
MicroRNAs
Ophthalmology
Lymphatic Endothelium
030104 developmental biology
Lymphatic system
chemistry
Immunology
Corneal neovascularization
government
Cancer research
Electrophoresis
Polyacrylamide Gel
Zdroj: Experimental Eye Research. 143:110-119
ISSN: 0014-4835
DOI: 10.1016/j.exer.2015.10.017
Popis: Neuropilin-2 (NP2), a high-affinity kinase-deficient co-receptor for vascular endothelial growth factor (VEGF)-C, is involved in embryonic vessel development, tumor growth, tumor lymphangiogenesis and metastasis. However, the pathological role of NP2 in other disorders, particularly under inflammatory lymphangiogenic conditions, remains largely unknown. In this study, we investigated the role of NP2 in inflammation-induced lymphangiogenesis in vivo using a lipopolysaccharide (LPS)-induced corneal neovascularization mouse model and in vitro using a macrophage-mouse lymphatic endothelial cell (mLEC) co-culture system. In the mouse model of LPS-induced inflammatory corneal neovascularization, NP2 and VEGFR-3 expression were rapidly up-regulated after LPS stimulation, and microRNA-mediated knockdown of NP2 significantly inhibited the up-regulation of VEGFR-3. Moreover, NP2 knockdown specifically inhibited the increase in the number of corneal lymphatic vessels but did not influence the increase in the number of blood vessels or macrophage recruitment induced by LPS. In a macrophage-LEC co-culture system, LPS up-regulated VEGFR-3 expression and induced mLEC migration and proliferation, and NP2 knockdown inhibited the up-regulation of VEGFR-3 expression and mLEC migration but not proliferation. Taken together, these results suggested that NP2 might be involved in the regulation of lymphangiogenesis via the regulation of VEGFR-3 expression during corneal inflammation. Therefore, NP2-targeted therapy might be a promising strategy for selective inhibition of inflammatory lymphangiogenesis in corneal inflammatory diseases, transplant immunology and oncology.
Databáze: OpenAIRE
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