Gold nanoparticles (GNPs) are widely used in life sciences and medicine due to their simple preparation, stable physical and chemical properties, controllable optical properties and no significant toxicity. However, in recent years, studies have found that there are still many uncertain
factors in the application of gold nanoparticles in the field of biomedicine, and there are few studies on the main excretion organs and kidneys of the body, especially the toxicological effects under the disease state have not been reported. Obviously, carrying out relevant research is of
great significance for accelerating the clinical application of GNPs. Chronic kidney disease (CKD) is a group of chronic progressive diseases that have high prevalence and high mortality and are serious threats to human life and health. Renal tubular injury and interstitial fibrosis are key
factors in renal dysfunction in chronic kidney disease. Drug and toxic kidney damage mostly involve renal tubular epithelial cells; hypoxia is the most common pathological condition of cells. In renal lesions, renal tubular epithelial cells often have hypoxia. Based on this, we propose the
hypothesis of this study: glomerular filtration membrane damage in kidney disease, GNPs increase in urine, followed by reabsorption of renal tubular epithelial cells, thereby causing damage to the latter; if accompanied by hypoxia, GNPs it will aggravate renal tubular epithelial cell damage
and promote tubulointerstitial fibrosis. In order to verify the above hypothesis, this study used a mouse model of adriamycin nephropathy and tubular epithelial cells and macrophages in vitro, and observed the damage of GNPs on renal tubular epithelial cells by various means, and explored
related mechanisms. The results show that under normal oxygen conditions, GNPs can induce autophagy after cell entry, which can damage damaged proteins and organelles to maintain cell survival. In the absence of oxygen, nanoparticles entering cells increase and induce excessive autophagy.
In the absence of oxygen, GNPs also aggregate in macrophages, which can cause decreased cell proliferation activity and induce activation of macrophage inflammasome, which induces inflammatory response: GNPs-induced secretion of hypoxic macrophages can be promoted.
LncRNA NEAT1 is involved in the protective effect of Klotho on renal tubular epithelial cells in diabetic kidney disease
