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11 August 2017 : Animal Research  

Function of NLRP3 in the Pathogenesis and Development of Diabetic Nephropathy

Ying Fu1BCDEF, Nannan Wu1CF, Dong Zhao1ACEF*

DOI: 10.12659/MSM.903269

Med Sci Monit 2017; 23:3878-3884

Abstract

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.

Keywords: Systemic Inflammatory Response Syndrome

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416