Bioinformatics-driven discovery of silica nanoparticles induces apoptosis and renal damage via the unfolded protein response in NRK-52E cells and rat kidney
Silica nanoparticles (SiNPs), a type of nanomaterial, have widespread applications in drug delivery and disease diagnosis. Despite their utility, SiNPs can lead to chronic kidney disease (CKD), which hinders their clinical translation. The molecular mechanisms responsible for SiNPs-induced renal toxicity are intricate and still need elucidation. To address this challenge, our study employed bioinformatics tools to predict potential mechanisms underlying renal damage caused by SiNPs. We identified 1627 up-regulated differentially expressed genes (DEGs) and 1334 down-regulated DEGs. Functional enrichment analysis and the protein-protein interaction (PPI) network revealed that SiNPs-induced renal damage is associated with apoptosis. Subsequently, we verified that SiNPs induce apoptosis in an in vitro model of NRK-52E cells via the unfolded protein response (UPR) in a dose-dependent manner. Furthermore, in an in vivo rat model, high-dose SiNPs administration via tracheal drip caused hyalinization in renal tubules, renal interstitial lymphocytic infiltration, and collagen fiber accumulation. Concurrently, we observed an increase in UPR-related proteins with the onset of renal damage. Thus, our study confirms that SiNPs induce apoptosis and renal damage through the unfolded protein response, adding to the theoretical understanding of SiNPs-related kidney damage and offering a potential target for preventing and treating kidney injuries in SiNPs clinical applications. Overall design: To analyze the molecular mechanisms responsible for SiNPs-induced renal toxicity