| First Author | Wang X | Year | 2020 |
| Journal | Am J Pathol | Volume | 190 |
| Issue | 3 | Pages | 642-659 |
| PubMed ID | 31972158 | Mgi Jnum | J:299725 |
| Mgi Id | MGI:6441834 | Doi | 10.1016/j.ajpath.2019.11.014 |
| Citation | Wang X, et al. (2020) miR-218 Expressed in Endothelial Progenitor Cells Contributes to the Development and Repair of the Kidney Microvasculature. Am J Pathol 190(3):642-659 |
| abstractText | Ischemia due to hypoperfusion is one of the most common forms of acute kidney injury. We hypothesized that kidney hypoxia initiates the up-regulation of miR-218 expression in endothelial progenitor cells (EPCs) to guide endocapillary repair. Murine renal artery-derived EPCs (CD34(+)/CD105(-)) showed down-regulation of mmu-Mir218-5p/U6 RNA ratio after ischemic injury, while in human renal arteries, MIR218-5p expression was up-regulated after ischemic injury. MIR218 expression was clarified in cell culture experiments in which increases in both SLIT3 and MIR218-2-5p expressions were observed after 5 minutes of hypoxia. ROBO1 transcript, a downstream target of MIR218-2-5p, showed inverse expression to MIR218-2-5p. EPCs transfected with a MIR218-5p inhibitor in three-dimensional normoxic culture showed premature capillary formation. Organized progenitor cell movement was reconstituted when cells were co-transfected with Dicer siRNA and low-dose Mir218-5p mimic. A Mir218-2 knockout was generated to assess the significance of miR-218-2 in a mammalian model. Mir218-2-5p expression was decreased in Mir218-2(-/-) embryos at E16.5. Mir218-2(-/-) decreased CD34(+) angioblasts in the ureteric bud at E16.5 and were nonviable. Mir218-2(+/-) decreased peritubular capillary density at postnatal day 14 and increased serum creatinine after ischemia in adult mice. Systemic injection of miR-218-5p decreased serum creatinine after injury. These experiments demonstrate that miR-218 expression can be triggered by hypoxia and modulates EPC migration in the kidney. |
