miR-129-5p and miR-130a-3p Regulate VEGFR-2 Expression in Sensory and Motor Neurons during Development

Abstract

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.

HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis

“…To identify the potential miRNA targets of HAGLR, we analyzed the HAGLR–miRNA interaction through the non-coding RNA database, starBase2.0. We observed miR-130a-3p, which plays an important role during neuron development and neuronal diseases [ 21 ], contains HAGLR binding sites ( Figure 2a ). We then evaluated the functional roles of miR-130a-3p during RA-induced neuron differentiation.…”

“…Moreover, the lncRNA–miRNA interaction has been shown to control vital functions during the molecular and cellular processes of human malignancies, including neuronal diseases [ 8 , 9 ]. A recent study reported that miR-130a-3p regulates VEGFR-2 expression in sensory and motor neurons during development [ 22 ]. Moreover, the miR-130a-3p/DAPK1 axis was known to regulate the pathophysiology of neonatal hypoxic-ischemia encephalopathy [ 23 ], suggesting miR-130-3p to be a potential therapeutic target for the hypoxic ischemia encephalopathy treatment.…”

Suppression of miR-130a-3p Attenuates Oxygen–Glucose Deprivation/Reoxygenation-Induced Dendritic Spine Loss by Promoting APP

“…Most studies have hitherto revealed that miRNAs function by binding to a specific sequence at the 3 UTR of their target mRNAs to induce degradation and translational repression of mRNAs (O'Brien et al, 2018). A previous study showed that in sensory dorsal root ganglia, VEGFR-2 expression increased during maturation and was accompanied by an overexpression of miR-130a-3p, which indicates that miR-130a-3p may affect neuron outgrowth through VEGFR-2 (Glaesel et al, 2020). However, VEGFR-2 was not significantly changed in the selected mRNA datasets of stroke brain tissue.…”

The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1

“…Recent literature has shown the potential roles of miRNAs, a type of small noncoding RNA in PF ( Dutta et al, 2019 ; Boateng and Krauss-Etschmann, 2020 ; Cho et al, 2020 ), which can regulate target genes or proteins through inflammatory responses related to mRNA degradation or translation inhibition. Among these miRNAs, miR-130a-3p observed in MSCs has been reported to have antitumor effects and has been used for treating neurological diseases ( Chen et al, 2010 ; Glaesel et al, 2020 ; Zhong et al, 2020 ). It has also been found that miR-130a-3p could exert cardioprotective effects through the induction of angiogenesis in ischemic hearts after myocardial infarction ( Moghaddam, et al, 2019 ).…”