Objective: 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.
Methods: 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.
Results: 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.
Conclusions: The data suggest that hemin caused multiple changes of gene expression in HK-2 cells, and ATF3 protects against hemin cytotoxicity.