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Integrin α5 Is Regulated by miR-218-5p in Endothelial Progenitor Cells
Jialing Liu1,2, Yi Li1, Lingna Lyu1,3
1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Journal of the American Society of Nephrology : JASN
|January 29, 2022
Summary
MicroRNA miR-218-5p regulates kidney endothelial progenitor cell (EPC) migration by targeting ITGA5. This finding is crucial for developing new therapies for microvascular kidney injury.
Area of Science:
- Renal cell biology
- Molecular and cellular cardiology
- Microvascular and endothelial biology
Background:
- Endothelial cell injury is a key factor in renal injury, with high prevalence of acute kidney injury (AKI) during COVID-19.
- Integrin α5 (ITGA5) is expressed in endothelial cells and vital for the Tie2 signaling pathway.
- While miR-218-5p is upregulated in endothelial progenitor cells (EPCs) post-hypoxia, its role in Tie2 signaling within EPCs remains unclear.
Purpose of the Study:
- To investigate the role of microRNA miR-218-5p in regulating endothelial progenitor cell (EPC) function in the kidney.
- To determine the molecular mechanisms by which miR-218-5p affects EPCs and their role in kidney repair.
Main Methods:
- Isolation of human kidney-derived EPCs (hkEPCs) and analysis of microRNA target transcripts.
- Utilizing a preclinical model of ischemic kidney injury to assess hkEPCs' impact on capillary repair.
- Employing a conditional knockout mouse model to examine the effects of deleting miR-218 in angioblasts.
Main Results:
- miR-218-5p was elevated in hkEPCs after ischemic preconditioning and directly bound to ITGA5 mRNA, reducing ITGA5 protein levels.
- miR-218-5p treatment decreased 42/44 MAPK phosphorylation by 73.6% in hkEPCs.
- Conditional knockout mice lacking miR-218 in CD309+ cells exhibited avascular glomeruli (homozygotes) or kidney injury susceptibility (heterozygotes); isolated mouse kidney EPCs showed high ITGA5 and reduced migration.
Conclusions:
- miR-218-5p critically regulates kidney EPC migration through ITGA5.
- These findings offer potential therapeutic strategies for microvascular kidney injury using cell-based delivery.
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