Journal article

Publication year: 2015

Pages: 1203-1217

Journal: Free Radical Biology and Medicine

Volume number: 89

ISSN: 0891-5849

eISSN: 1873-4596

DOI Link: https://doi.org/10.1016/j.freeradbiomed.2015.10.423

Publisher: Elsevier

Abstract: 

Objective: Cell injury releases nucleic acids supporting inflammation and stem cell activation. Here, the impact of extracellular ribonucleic acid, especially transfer RNA (ex-tRNA), on vasculogenesis and leukopoiesis of mouse embryonic stem (ES) cells was investigated.

Approach and results: ex-tRNA, whole cell RNA and ribosomal RNA (ex-rRNA) but not DNA increased CD31-positive vascular structures in embryoid bodies. Ex-tRNA and ex-rRNA increased numbers of VEGFR2(+), CD31(+) and VE-cadherin(+) vascular cells as well as CD18(+), CD45(+) and CD68(+) cells, indicating leukocyte/macrophage differentiation. This was paralleled by mRNA and protein expression of hypoxiainducible factor-l alpha (HIF-l alpha), vascular endothelial growth factor-165 (VEGF(165)) and neuropilin 1 (NRP1), phosphorylation of phosphatidyl inositol 3-kinase (PI3K) and VEGF receptor 2 (VEGFR2) as well as mRNA expression of ox-smooth muscle actin (alpha-SMA). ex-tRNA was taken up by endosomes, increased expression of the pro-angiogenic semaphorin B4 receptor plexin B1 as well as the ephrin-type B receptor 4 (EphB4) and ephrinB2 ligand and enhanced cell migration, which was inhibited by the VEGFR2 antagonist 5U5614 and the PI3K inhibitor LY294002. This likewise abolished the effects of ex-tRNA on vasculogenesis and leukopoiesis of ES cells. Ex-tRNA increased NOX1,NOX2,NOX4 and DUOX2 mRNA and boosted the generation of superoxide and hydrogen peroxide which was inhibited by radical scavengers, the NADPH oxidase inhibitors apocynin, VAS2870, ML171, and plumbagin as well as shRNA silencing of NOX1 and NOX4.

Conclusions: Our findings indicate that ex-tRNA treatment induces vasculogenesis and leukopoiesis of ES cells via superoxide/hydrogen peroxide generated by NADPH oxidase and activation of VEGFR2 and PI3K. (C) 2015 Elsevier Inc. All rights reserved.

Harvard Citation style: Sharifpanah, F., De Silva, S., Bekhite, M., Hurtado-Oliveros, J., Preissner, K., Wartenberg, M., et al. (2015) Stimulation of vasculogenesis and leukopoiesis of embryonic stem cells by extracellular transfer RNA and ribosomal RNA, Free Radical Biology and Medicine, 89, pp. 1203-1217. https://doi.org/10.1016/j.freeradbiomed.2015.10.423

APA Citation style: Sharifpanah, F., De Silva, S., Bekhite, M., Hurtado-Oliveros, J., Preissner, K., Wartenberg, M., & Sauer, H. (2015). Stimulation of vasculogenesis and leukopoiesis of embryonic stem cells by extracellular transfer RNA and ribosomal RNA. Free Radical Biology and Medicine. 89, 1203-1217. https://doi.org/10.1016/j.freeradbiomed.2015.10.423