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) are nanomaterials with widespread applications in drug delivery and disease diagnosis. Despite their utility, SiNPs can cause chronic kidney disease, hindering their clinical translation. The molecular mechanisms underlying SiNP-induced renal toxicity are complex and require further investigation. To address this challenge, we employed bioinformatics tools to predict the potential mechanisms underlying renal damage caused by SiNPs. We identified 1627 upregulated differentially expressed genes (DEGs) and 1334 downregulated DEGs. Functional enrichment analysis and protein-protein interaction network revealed that SiNP-induced renal damage is associated with apoptosis. Subsequently, we verified that SiNPs induced 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 SiNP administration via tracheal drip caused hyalinization of the renal tubules, renal interstitial lymphocytic infiltration, and collagen fiber accumulation. Concurrently, we observed an increase in UPR-related protein levels at the onset of renal damage. Thus, our study confirmed that SiNPs induce apoptosis and renal damage through the UPR, adding to the theoretical understanding of SiNP-related kidney damage and offering a potential target for preventing and treating kidney injuries in SiNP clinical applications.