Exosomal lincRNA-p21/AIF-1 promoted inflammation of human tubular epithelial cell via CMPK2/NLRP3 pathway in urate nephropathy

Abstract

Abstract Background and hypothesis Urate nephropathy, a common complication of hyperuricemia, has garnered increasing attention worldwide. However, the exact pathogenesis of this condition remains unclear. Currently, inflammation is widely accepted as the key factor in urate nephropathy. Therefore, the aim of this study was to elucidate the mechanism of exosomal lincRNA-p21/AIF-1 in urate nephropathy. Methods This study evaluated the effects of exosomes using clinical data collected from patients with urate nephropathy and human renal tubular epithelial cells (HK2) cultured with different concentrations of urate. Results In the clinical research section, the level of exosomal lincRNA-p21/AIF-1 in the urine of patients with hyperuricemia or urate nephropathy was found to be increased, particularly in patients with urate nephropathy. In vitro study section, the levels of exosomes, inflammation, autophagy, and apoptosis were increased in HK2 cells induced by urate. Additionally, the expressions of lincRNA-p21, AIF-1, CMPK2, and NLRP3 were upregulated in exosomes and HK2 cells. Furthermore, manipulating the activity of lincRNA-p21, AIF-1, CMPK2, and NLRP3 through overexpression or interference vectors promoted inflammation, autophagy, and apoptosis in HK2 cells induced by urate. Conclusions: In conclusion, the aforementioned results suggested that exosomal lincRNA-p21/AIF-1 induces inflammation via the CMPK2/NLRP3 pathway, thereby promoting autophagy and apoptosis in renal tubular epithelial cells induced by urate.