Artikel
Potential role of brain injury associated miR-451 in neurogenic processes in vitro
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Veröffentlicht: | 13. Mai 2014 |
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Gliederung
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Objective: Micro-RNAs (miR) are small, endogenous noncoding RNA molecules, which regulate gene expression posttranscriptionally. We have recently shown that miR-451 is present in microparticles (MPs) isolated from cerebrospinal fluid (CSF) of traumatic brain injured (TBI) patients but not in the CSF of non-injured controls. Uptake of MPs derived from CSF of TBI patients by neural stem cells in vitro results in miR-451 specific down-regulation of FGFR1 (Fibroblast growth factor receptor 1) and CD133. These factors are correlated with injury induced neurogenesis. High cerebral miR-451 levels might therefore negatively regulate early neurogenic processes and could be associated to more mature differentiation states. Therefore we analyse the role of miR-451 in neuronal differentiation in vitro.
Method: NT-2 cells (Ntera-2 cl.D1) were transduced with miR-451 overexpression vectors using lentiviruses. Neuronal differentiation was induced by supply of retinoic acid and cells were analysed at different developmental time points. Cell migration and development was monitored using CellIQ; miRNA expression using PCR; Immunohistochemistry was performed to visualize neuronal extensions.
Results: Overexpression of miR-451 results in a delay of gap closure in scratch assays and a significant elongation of cells. Expression levels of miR-451 significantly increase during late stages of neuronal differentiation in NT-2 cells. Neurite outgrowth from NT-2 neurospheres and mobility of the precursor cells was significantly enhanced in miR-451 overexpressing cells.
Conclusions: Increased miR-451 expression levels during neuronal differentiation in vitro, enhanced elongation of miR-451 overexpressing cells and augmented outgrowth of neurites during neuronal differentiation indicate a role of miR-451 in neurogenic maturation processes.