Abstract: FR-PO939
The Role of Mir218 in the Function of the Renal Vasculature
Session Information
- Development, Stem Cells, Regenerative Medicine - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 501 Development, Stem Cells, and Regenerative Medicine: Basic
Authors
- Yin, Wenqing, Brigham and Women's Hospital , Boston, Massachusetts, United States
- Siedlecki, Andrew M., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background
Vascular density is critical to normal kidney function. Reduced renal capillary number is associated with hypertension, chronic kidney disease, and kidney failure. Endothelial progenitor cells play a pivotal role in the construction of endocapillaries as well as their repair following ischemic injury. The function of endothelial progenitor-derived cells is dependent on cellular programs regulated by select microRNA. Mir218 directs retinal endothelial cell migration and motor neuron development. The role of mir218 in the function of the renal vasculature is widely unknown.
Methods
With CRISPR/Cas9 gene editing, we created an animal model, with germ-line miR-218-2 deletion (miR218-/-). These miR218-/- mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) for 26 minutes, or sham surgery at 3 months of age and then evaluation the kidney function at 48 and 96 hours. Immunofluorescence staining of CD31 was assessed for the vascular density in this context.
Results
Following renal-specific ischemia/reperfusion injury, miR218-/- mice (n=6) were slow to recover renal function after 48 and 96 hours. There was a 20% of miR218-/- mice suffered fulminant renal failure and died within 96 hours. In miR218-/- mice, a lower vascular density in kidney with reduced renal capillary number were identified by CD31 staining.
Conclusion
With CRISPR/Cas9 gene editing approach to knock out miR-218-2 in the regulation of endothelial cell migration, we demonstrate for the first time the critical role of mir218 in the function of the renal vasculature.
Funding
- Other U.S. Government Support