Molecular Mechanics Research Papers - Academia.edu (original) (raw)

1,3-Dinitrobenzene (1,3-DNB) specifically injures Sertoli cells and induces testicular toxicity by disrupting the key function of these cells. To clarify the molecular mechanism underlying 1,3-DNB’s action on Sertoli cells, we analyzed gene expression profiles of TM4 mouse Sertoli cells after chemical treatment. In total, 1,203 genes were identified as either up- or down-regulated, with greater than 1.5-fold changes (P<0.05). Based on k-means clustering, genes that were differentially expressed in a time-dependent manner were identified; then biofunction and canonical pathways were analyzed using Ingenuity Pathways Analysis. Genes related to axonal guidance, Nrf2-mediated oxidative stress response, protein ubiquitination, and tight junction signaling pathways were identified in either time-specifically or time-dependently regulated groups. The transcription levels of genes related to tight junction signaling pathways (Mpp5, F11r, Prkcz, Magi2, and Tgfb2) and genes encoding junction proteins (Ocln, Tjp1, Tjp2, Gja1, and Gjd2) were validated in 1,3-DNB-treated and 2,5-hexanedione-treated TM4 cells by quantitative real-time polymerase chain reaction. Comprehensive gene expression profiling of 1,3-DNB-treated TM4 cells and subsequent canonical pathway analyses provided valuable information regarding the molecular mechanism of cell death and cell interaction in TM4 mouse Sertoli cells after 1,3-DNB exposure.