Global transcriptional analysis of human FHs 74 Int intestinal epithelial cells after exposure to advanced glycation end products

Advanced glycation end products (AGEs) are formed during the thermal processing of food and have been implicated in the pathogenesis of a series of chronic inflammatory diseases. AGEs are hypothesized to interact with the intestinal epithelium upon the ingestion of thermally processed food, however, their direct effect on intestinal epithelial cells is poorly understood. This study investigates transcriptomic changes in human intestinal epithelial FHs 74 Int cells after exposure to methylglyoxal-modified human serum protein (AGE-HS), S100A12, a known RAGE ligand, and unmodified human serum proteins (HS) in comparison to PBS treated cells. Surprisingly, AGE-HS treatment did not result in significant differential gene expression at standard analysis thresholds, while unmodified HS induced minor transcriptional changes. S100A12 also elicited no significant gene expression alterations. However, GSEA revealed subtle but coordinated changes – AGE-HS treatment induced downregulation of gene sets linked to MYC, interferon responses, and oxidative phosphorylation, paralleling some effects observed with S100A12. Also, KEGG pathway analysis revealed partial overlap between responses to AGE-HS and S100A12 affecting pathways associated with oxidative phosphorylation and neurodegenerative diseases such as Alzheimer, Parkinson, and Huntington disease. This study provides the first global transcriptomic analysis of intestinal epithelial cells treated with AGE-modified proteins. The effects were less pronounced than expected, thus, these data challenge previous reports of robust AGE-induced inflammatory and proliferative effects and emphasize the importance of rigorous endotoxin testing and the use of appropriate controls.