Microarray Analysis of Altered Gene Expression and the Role of ATF3 in HK-2 Cells Treated with Hemin

To identify gene expression changes and the role of activating transcription factor 3 (ATF3) in hemin toxicity in renal tubular epithelial cells, then elucidate molecular mechanisms of hemin toxicity on renal tubular epithelial cells.An oligo array comprising 35,035 genes was used to compare differential gene expression in hemin-treated and non-treated HK-2 cells (human renal proximal tubular epithelial cells), and the role of ATF3 in hemin toxicity was assessed using siRNA technique.A total of 128 mRNAs were at least twofold up-regulated and 101 mRNAs were at least twofold down-regulated after hemin treatment. Expression levels of ATF3, heat shock protein 70, c-fos, and c-jun were remarkably increased. Hemin also suppressed nuclear factor-kappa B inhibitor α, β-2 adrenergic receptor, and interleukin-6 mRNA amounts more than twofold. We further demonstrated the protective role of ATF3 in hemin cytotoxicity.The data suggest that hemin caused multiple changes of gene expression in HK-2 cells, and ATF3 protects against hemin cytotoxicity.