Function of NLRP3 in the Pathogenesis and Development of Diabetic Nephropathy

BACKGROUND The aim of this research was to study the function of NLRP3 in the pathogenesis and development of diabetic nephropathy (DN). MATERIAL AND METHODS We compared the expression of NLRP3-related protein in human glomerular mesangial cells under high glucose conditions at different times and in rats with DN of different ages. We also compared changes in IL-18 and IL-1β expression levels at different stages of DN. RESULTS After six hours, 12 hours, and 24 hours of high glucose stimulation, the secretion of IL-1β in human glomerular mesangial cells, compared to unstimulated cells, was 1.85-fold, 3.04-fold, and 4.14-fold; the expression of NLRP3 increased by 2.20-fold, 4.62-fold, and 8.32-fold; and the expression of caspase-1 was increased by 1.60-fold, 2.72-fold, and 3.67-fold. The expression levels of nephrin in eight-week-old and 12-week-old DN rats compared to 4-week rats were 49.60% and 21.20%, respectively. The IL-1β levels compared to four-week DN rats were 2.57-fold and 4.17-fold, respectively; NLRP3 levels were 1.29-fold and 2.17-fold respectively, and caspase-1 levels were 3.37-fold and 4.16-fold, respectively. The serum levels of IL-18 and IL-1β in the DN group were the highest at 218.53±30.69 pg/mL and 62.47±9.36 pg/mL, respectively; followed by the mild DN group at 177.07±32.88 pg/mL and 28.13±5.37 pg/mL, respectively, with the diabetic mellitus (DM) group having the lowest levels at 141.47±9.49 pg/mL and 15.53±3.26 pg/mL, respectively. The healthy control group levels were 99.40±22.72 pg/mL and 12.40±5.08 pg/mL, respectively. CONCLUSIONS NLRP3 and high glucose activation may participate in the occurrence and development of DN by mediating the inflammatory response.