Activation of Toll-like receptor 3 promotes pathological corneal neovascularization by enhancement of SDF-1-mediated endothelial progenitor cell recruitment

Autor: Ruijuan Zhao, Jing Zhang, Jianping Chen, Yan Wang, Shao Bo Su, Hongyan Zhou, Jiayi Jin
Rok vydání: 2019
Předmět:
0301 basic medicine
genetic structures
medicine.medical_treatment
Administration
Ophthalmic
chemical and pharmacologic phenomena
Real-Time Polymerase Chain Reaction
Endothelial progenitor cell
Cornea
Neovascularization
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Cell Movement
Burns
Chemical
medicine
Animals
Sodium Hydroxide
Corneal Neovascularization
Progenitor cell
Fluorescent Antibody Technique
Indirect
Receptor
Endothelial Progenitor Cells
Toll-like receptor
Chemistry
medicine.disease
Chemokine CXCL12
eye diseases
Sensory Systems
Toll-Like Receptor 3
Mice
Inbred C57BL
Disease Models
Animal
Eye Burns
Ophthalmology
Poly I-C
030104 developmental biology
Cytokine
Corneal neovascularization
TLR3
030221 ophthalmology & optometry
Cancer research
sense organs
medicine.symptom
Signal Transduction
Zdroj: Experimental Eye Research. 178:177-185
ISSN: 0014-4835
Popis: Toll-like receptors (TLRs) play an important role in inflammatory and immunological responses, which are intimately related to neovascularization. However, the precise mode of action of TLR3 in neovascularization still remains ambiguous. In this study, we sought to investigate the role of TLR3 in pathological corneal neovascularization (CNV) using a mouse model of alkali-induced CNV. CNV was attenuated in TLR3-deficient mice, and the absence of TLR3 led to decreased production of stromal cell-derived factor 1 (SDF-1), a well-characterized cytokine that regulates the recruitment of endothelial progenitor cells (EPCs) to the sites of neo-angiogenic niches in the injured tissues. Topical administration of polyinosinic-polycytidylic acid [poly (I:C)], a synthetic ligand for TLR3, to the injured cornea promoted CNV in wild type (WT) mice but not in TLR3-deficient mice. In addition, the effect of poly (I:C) on WT mice was abolished by addition of SDF-1 receptor antagonist AMD 3100. Furthermore, poly (I:C) treatment in vitro enhanced the migration of EPCs, whereas the enhanced migration was abolished by AMD 3100. These results indicate an essential role of TLR3 signalling in CNV that involves upregulating SDF-1 production and recruiting EPCs to the sites of injury for neovascularization. Thus, targeting the TLR3 signalling cascade may constitute a novel therapeutic approach for treating neovascularization-related diseases.
Databáze: OpenAIRE
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