Details

Autor(en) / Beteiligte

• Wang, Xiaojie
• Liu, Jialing
• Yin, Wenqing
• Abdi, Farhiya
• Pang, Paul D.
• Fucci, Quynh-Anh
• Abbott, Molly
• Chang, Steven L.
• Steele, Graeme
• Patel, Ankit
• Mori, Yutaro
• Zhang, Aifeng
• Zhu, Shikai
• Lu, Tzong-Shi
• Kibel, Adam S.
• Wang, Bin
• Lim, Kenneth
• Siedlecki, Andrew M.

Titel

miR-218 Expressed in Endothelial Progenitor Cells Contributes to the Development and Repair of the Kidney Microvasculature

Ist Teil von

• The American journal of pathology, 2020-03, Vol.190 (3), p.642-659

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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.