miR-129-5p and miR-130a-3p regulate VEGFR-2 expression in sensory and motor neurons during development
- The wide-ranging influence of vascular endothelial growth factor (VEGF) within the central (CNS) and peripheral nervous system (PNS), for example through effects on axonal growth or neuronal cell survival, is mainly mediated by VEGF receptor 2 (VEGFR-2). However, the regulation of VEGFR-2 expression during development is not yet well understood. As microRNAs are considered to be key players during neuronal maturation and regenerative processes, we identified the two microRNAs (miRNAs)—miR-129-5p and miR-130a-3p—that may have an impact on VEGFR-2 expression in young and mature sensory and lower motor neurons. The expression level of VEGFR-2 was analyzed by using in situ hybridization, RT-qPCR, Western blot, and immunohistochemistry in developing rats. microRNAs were validated within the spinal cord and dorsal root ganglia. To unveil the molecular impact of our candidate microRNAs, dissociated cell cultures of sensory and lower motor neurons were transfected with mimics and inhibitors. We depicted age-dependent VEGFR-2 expression in sensory and lower motor neurons. In detail, in lower motor neurons, VEGFR-2 expression was significantly reduced during maturation, in conjunction with an increased level of miR-129-5p. In sensory dorsal root ganglia, VEGFR-2 expression increased during maturation and was accompanied by an overexpression of miR-130a-3p. In a second step, the functional significance of these microRNAs with respect to VEGFR-2 expression was proven. Whereas miR-129-5p seems to decrease VEGFR-2 expression in a direct manner in the CNS, miR-130a-3p might indirectly control VEGFR-2 expression in the PNS. A detailed understanding of genetic VEGFR-2 expression control might promote new strategies for the treatment of severe neurological diseases like ischemia or peripheral nerve injury.
Author: | Kevin GläselGND, Caroline MayORCiDGND, Katrin Marcus-AlicORCiDGND, Veronika MatschkeORCiDGND, Carsten TheißORCiDGND, Verena TheisGND |
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URN: | urn:nbn:de:hbz:294-78093 |
DOI: | https://doi.org/10.3390/ijms21113839 |
Parent Title (English): | International journal of molecular sciences |
Publisher: | MDPI |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/01/29 |
Date of first Publication: | 2020/05/28 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds VEGFR-2; microRNA; motor neurons; nervous system; neuronal maturation; sensory neurons |
Volume: | 21 |
Issue: | 11, Artikel 3839 |
First Page: | 3839-1 |
Last Page: | 3839-19 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Medizinisches Proteom-Center |
Institut für Anatomie, Abteilung für Cytologie | |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |