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MicroRNA-188-5p regulates contribution of bone marrow-derived cells to choroidal neovascularization development by targeting MMP-2/13
- Source :
- Experimental eye research. 175
- Publication Year :
- 2018
-
Abstract
- Our previous investigations have shown that bone marrow-derived cells (BMCs), including mesenchymal stem cells (MSCs), contribute to the development of choroidal neovascularization (CNV) as sources of cells and angiogenic factors. Two main steps for circulating BMCs to integrate into CNV lesions are extracellular matrix remodeling and consequential cell migration. MicroRNAs (miRNAs) were found to be involved in CNV development; however, little is known about whether miRNAs regulate the contribution of BMCs to CNV. In the present study, we found that the expression of miR-188-5p was decreased in cultured hypoxic MSCs and BMCs within laser-induced CNV in mice. Matrix metalloproteinase 2 (MMP-2) and MMP-13 were both discovered as targets of miR-188-5p by bioinformatics predictions and dual-luciferase reporter system. Accordingly, increased expression of MMP-2/13 was found in hypoxic MSCs and BMCs in CNV lesions. Furthermore, miR-188-5p mimic transfection caused downregulation of MMP-2/13 in hypoxic MSCs and decreased tube formation of co-cultured vascular endothelial cells. Intravitreal injections of a miR-188-5p agomir attenuated the severity of CNV and inhibited the migration of BMCs into CNV lesions in mice. Our study suggests that miR-188-5p regulates the contribution of BMCs to CNV development by targeting MMP-2/13-mediated extracellular matrix degeneration, and miR-188-5p serves as a therapeutic target to treat CNV-related diseases.
- Subjects :
- 0301 basic medicine
genetic structures
Blotting, Western
Green Fluorescent Proteins
Bone Marrow Cells
Mice, Transgenic
Matrix metalloproteinase
Real-Time Polymerase Chain Reaction
Transfection
Cell Line
Extracellular matrix
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Matrix Metalloproteinase 13
medicine
Animals
Fluorescent Antibody Technique, Indirect
Cells, Cultured
In Situ Hybridization, Fluorescence
Tube formation
business.industry
Mesenchymal stem cell
Cell migration
Mesenchymal Stem Cells
Macaca mulatta
eye diseases
Sensory Systems
Choroidal Neovascularization
Mice, Inbred C57BL
Ophthalmology
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Choroidal neovascularization
Gene Expression Regulation
030221 ophthalmology & optometry
Cancer research
Matrix Metalloproteinase 2
sense organs
Bone marrow
Endothelium, Vascular
medicine.symptom
business
Subjects
Details
- ISSN :
- 10960007
- Volume :
- 175
- Database :
- OpenAIRE
- Journal :
- Experimental eye research
- Accession number :
- edsair.doi.dedup.....92deebd5aae1733d3ddd748f0d4ddc0b