FIG. 4.

Vitamin C upregulates proliferation-related genes. Microarray was used to clarify the vitamin C target genes that mediate ASC stimulation, and Fos was identified as a key transcription factor. (A) Vitamin C treatment significantly upregulated 123 genes (>2-fold, P<0.05), but downregulated 24 genes. (B) Analysis of gene ontology using the differentially expressed genes (DEGs) demonstrated that genes related to cell proliferation (35%), transcription (16%), and differentiation were primarily upregulated by vitamin C treatment. (C) Using these altered proliferation-related genes, a possible interaction network among the DEGs was analyzed by STRING 9.05 (http://string.embl.de) and plotted using Cytoscape 2.8.3. White circles indicate the upregulated genes, while the black circles indicate the downregulated genes. (D) Transfection of Fos siRNA significantly reduced the proliferation of ASCs, whereas transfection of E2F2 did not. (E) Further, Fos silencing reduced the vitamin C-induced E2F2 mRNA expression. Data are mean±STD (n.s., not significant; **P<0.01, Student's t-test).