MicroRNA-188-5p regulates contribution of bone marrow-derived cells to choroidal neovascularization development by
Huiyuan Hou1, Fan Gao2, Hongliang Liang3
1Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China; Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, CA, United States.
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.
Insights
MicroRNA-188-5p (miR-188-5p) regulates bone marrow cells
Area of Science:
- Ophthalmology
- Stem Cell Biology
- Molecular Biology
Background:
- Bone marrow-derived cells (BMCs), including mesenchymal stem cells (MSCs), contribute to choroidal neovascularization (CNV).
- Extracellular matrix remodeling and cell migration are key steps for BMCs integrating into CNV lesions.
- MicroRNAs (miRNAs) are implicated in CNV, but their role in BMC contribution is unclear.
Purpose of the Study:
- To investigate the role of miR-188-5p in regulating BMC contribution to CNV.
- To identify the molecular targets of miR-188-5p in this process.
Main Methods:
- Assessed miR-188-5p expression in hypoxic MSCs and BMCs in a mouse model of laser-induced CNV.
- Utilized bioinformatics and dual-luciferase reporter assays to identify MMP-2 and MMP-13 as miR-188-5p targets.
- Transfected MSCs with miR-188-5p mimic and assessed effects on MMP expression and endothelial cell tube formation.
- Administered miR-188-5p agomir via intravitreal injection in mice with CNV.
Main Results:
- miR-188-5p expression was decreased in hypoxic MSCs and BMCs in CNV lesions.
- MMP-2 and MMP-13 were validated as direct targets of miR-188-5p.
- miR-188-5p mimic transfection downregulated MMP-2/13 and reduced endothelial cell tube formation.
- Intravitreal miR-188-5p agomir attenuated CNV severity and inhibited BMC migration.
Conclusions:
- miR-188-5p regulates BMC contribution to CNV by targeting MMP-2/13-mediated extracellular matrix degradation.
- miR-188-5p represents a potential therapeutic target for treating CNV-related diseases.
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