Silica nanoparticles induce apoptosis via the unfolded protein response in NRK-52E cells and rat kidney

Silica nanoparticles (SiNPs) have multiple applications, particularly in the field of biomedical science. However, SiNPs can cause a multitude of diseases, including chronic kidney disease (CKD). The molecular mechanism of renal toxicity caused by SiNPs is complex and remains to be clarified. Therefore, we examined the role and mechanism of apoptosis via the unfolded protein response (UPR) induced by SiNPs. We utilized an in vitro model of NRK-52E cells and an in vivo rat model with SiNPs administered via tracheal drip. After the NRK-52E cells were exposed to SiNPs, cell viability decreased; the mitochondrial membrane potential, calcium content, reactive oxygen species, and apoptosis rate increased; and light microscopy revealed cell damage. Meanwhile, apoptosis, the UPR, and oxidative stress-related proteins were all increased in NRK-52E cells. Moreover, an increase in the concentration of SiNPs was positively correlated with renal damage, as detected by light microscopy and transmission electron microscopy. As the SiNP concentration increased, apoptosis, the UPR, and oxidative stress-related proteins increased and the activity of antioxidant enzymes decreased in rat kidney. We conclude that the UPR plays a key role in apoptosis induced by SiNPs in the kidney.