Journalartikel

Jahr der Veröffentlichung: 2016

Seiten: 3096-3105

Zeitschrift: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Bandnummer: 1863

Heftnummer: 12

ISSN: 0167-4889

eISSN: 0006-3002

DOI Link: https://doi.org/10.1016/j.bbamcr.2016.10.001

Verlag: Elsevier

Abstract: 

Objectives: Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies.

Methods and results: Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB) as evaluated by Western blot and real time RT-PCR. In contrast ephrin type 4 receptor B (EphB4) expression was down regulated upon mechanical strain, indicating an arterial-type differentiation. Robo1 protein expression was modestly increased with no change in mRNA expression. Mechanical strain increased intracellular calcium as well as reactive oxygen species (ROS) and nitric oxide (NO). Mechanical strain-induced vasculogenesis was abolished by the NOS inhibitor L-NAME, the NADPH oxidase inhibitor VAS2870, upon chelation of intracellular calcium by BAPTA as well as upon siRNA inactivation of ephrin B2, NRP1 and robo4. BAPTA blunted the strain-induced expression of angiogenic growth factors, the increase in NO and ROS as well as the expression of NRP1, sem4D and plexinB1, whereas ephrin B2, EphB4 as well as robo1 and robo4 expression were not impaired.

Conclusions: Mechanical strain stimulates vasculogenesis of ES cells by the intracellular messengers ROS, NO and calcium as well as by upregulation of angiogenesis guidance molecules and the angiogenic growth factors VEGF, FGF-2 and PDGF-BB. (C) 2016 Elsevier B.V. All rights reserved.

Harvard-Zitierstil: Sharifpanah, F., Behr, S., Wartenberg, M. and Sauer, H. (2016) Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1863(12), pp. 3096-3105. https://doi.org/10.1016/j.bbamcr.2016.10.001

APA-Zitierstil: Sharifpanah, F., Behr, S., Wartenberg, M., & Sauer, H. (2016). Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1863(12), 3096-3105. https://doi.org/10.1016/j.bbamcr.2016.10.001