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Objective Nerve regeneration is a complex biological phenomenon incorporating multiple cells, growth factors and an extracellular matrix.MiRNAs are endogenous, non-coding 21-to 23-nucleotide small RNA molecules that regulate gene expression by binding to the 3 untranslated region of target mRNAs, leading to their translational inhibition or degradation.The present study is to explore whether miRNAs are capable of mobilizing the intrinsic capacity for neurite growth and promoting axon regeneration.Methods We analyzed the changes in miRNA and mRNA expression in the DRG, following sciatic nerve transection, using microarray and bioinformatics analysis.To validate the microarray platform, we assessed the expression by real time Taqman PCR.To validate the target, we performed luciferase reporter assay.Further, we transfected the miRNA-21 mimics and PITX2 siRNA to the cultured DRG neurons.Results (1) The bioinformatics analysis indicated that miRNA-21 play important roles in regulating nerve regeneration via the target PITX2 in the network.(2) miRNA-21 is inversely correlated with PITX2 expression in DRG tissues.(3) In the cultured DRG neurons, miRNA-21 promotes neurite growth and inhibits PITX2 expression.Transfection of PITX2 siRNA also promotes neurite growth.Conclusion miRNA-21 is significantly up-regulated following sciatic nerve injury and promotes neurite growth by targeting PITX2.