Microarray-based identification of nerve growth-promoting genes in neurofibromatosis type I

Abstract

Abstract. As a genetic disease, neurofibromatosis type 1 (NF1) is characterized by abnormalities in multiple tissues derived from the neural crest, including neoplasms in the ends of the limbs. The exact mechanism of nerve growth in NF1 is unclear. In the present study, the gene expression profile of nerves in healthy controls and NF1 patients with macrodactylia of the fingers or toes were analyzed in order to identify possible genes associated with nerve growth. The Whole Human Genome Microarray was selected to screen for different gene expression profiles, and the result was analyzed with Feature Extraction software. The target genes were verified at the transcriptional and translational levels by reverse transcription-polymerase chain reaction and western blotting, respectively. A common set of 28 genes were identified to be changed >5-fold in the NF1 patients compared with the healthy controls. Among them, the metastasis-associated genes, lymphocyte function-associated antigen 1, C-X-C chemokine receptor type 4 and intracellular adhesion molecule 1, and the inflammatory cytokines, interleukin (IL) 1β, IL-6 and IL-8, were downregulated significantly. Mainly genes that changed >10-fold were analyzed in this study, and HOXC8 demonstrated activity in promoting nerve growth. Through the analysis of the mRNA expression of the nerves in the NF1 patients, target molecules contributing to nerve growth during NF1 development were investigated, which aided in improving our understanding of this disease, and may provide a novel direction for nerve repair and regeneration.