Influence of XXXX Aligned Nanofibers on PC12 Differentiation.

@entity15274 @entity72195 @entity2508 @entity72197 @entity7049 @entity12704 @entity9270 @entity72196 @entity2270
The aim of this study was to unveil the mechanism by which aligned nanofibers influence neuronal differentiation. PC12 cells were seeded on three different @entity7049 ( @entity15274 ) substrates ( @entity15274 films (control), electrospun @entity15274 random nanofibers (RF) and electrospun @entity15274 aligned nanofibers (AF)). Subsequently, cellular experiments, cDNA microarrays and molecular biological approaches were employed to investigate the impacts of the different @entity15274 substrates on PC12 cell differentiation. Scanning electron microscope observation revealed that neurite outgrowth in the AF group was parallel to the direction of nanofiber alignment and that the filopodias at the neurite tips spread along the aligned nanofiber @entity2270 . Meanwhile, both neurite length and the expression of @entity9270 (a neuronal differentiation marker gene) were higher in the AF group than those in the control and RF groups. These results suggested that the @entity15274 aligned nanofibers enhanced PC12 cell differentiation. cDNA microarray experiment revealed that 876 and 1937 genes had significantly changed expression in the RF and AF groups, respectively. Based on gene ontology analysis, 493 and 1193 differentially expressed genes involved in neuronal differentiation were found in the RF and AF groups, respectively. Pathway analysis showed that the @entity15274 aligned nanofibers mainly mediated their effects via integrin-mediated pathways. qRT-PCR and western blotting assays further confirmed that gene and protein expression levels in the integrin-mediated FAK-MEK-ERK pathway (e.g., @entity72195 , @entity72196 , phosphorylated- @entity2508 ) were enhanced by the @entity15274 aligned nanofibers. Both PC12 cell differentiation and the expressions of genes and proteins in the integrin-mediated FAK-MEK-ERK pathway were inhibited when integrins were blocked by the @entity12704 GRGDS. In addition, the @entity72197 gene was found to be involved in @entity15274 aligned nanofibers' promotion of PC12 cell differentiation. Taken together, the results suggested that @entity15274 aligned nanofibers might cooperate with nerve growth factor (NGF) to induce PC12 cell differentiation by activating the integrin-mediated FAK-MEK-ERK pathway and the @entity72197 gene.
