Corn Silk Polysaccharides Before and After Selenization Reduced Calcium Oxalate Crystal-Induced HK-2 Cells Pyroptosis by Inhibiting the NLRP3-GSDMD Signaling Pathway

Jin Han,1 Xin-Yi Tong,2 Yu-Yun Zheng,2 Jia-Hui Cheng,1 Jian-Ming Ouyang,2 Ke Li3 1Department of Nephrology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Institute of Biomineralization and Lithiasis Research, College of Chemistry and Materials Science; Jinan University, Guangzhou, 510632, People’s Republic of China; 3Core Research Laboratory, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Jian-Ming Ouyang, Email [email protected]; Ke Li, Email [email protected]: Pyroptosis is a new type of programmed cell death associated with many inflammatory diseases. Polysaccharides have anti-inflammatory effects. In this study, we investigated whether corn silk polysaccharides (DCSP) before and after selenization (Se-DCSP) can reduce the renal tubule pyroptosis induced by calcium oxalate crystals.Methods: HK-2 cells were exposed to calcium oxalate monohydrate with a size of 3 μm (COM-3μm) to establish a pyroptosis model. The degree of cell damage was determined by detecting cell viability, reactive oxygen species (ROS), and lactate dehydrogenase (LDH) content. The proportion of pyroptosis cells was quantitatively detected by Caspase-1/PI double staining. The expression levels of NLRP3, GSDMD, IL-18, and IL-1β were detected by confocal microscopy and Western blot analyses.Results: DCSP and Se-DCSP can reduce the secretion of inflammatory factors IL-1β/18 related to pyroptosis by reducing cell damage and oxidative stress, as well as down-regulate the expression of Caspase-1, NLRP3, GSDMD, and TNF-α, repair damaged cells, and inhibit pyroptosis in HK-2 cells. The inhibitory effect of selenized polysaccharide was significantly enhanced compared with that before selenification.Conclusion: Se-DCSP can inhibit pyroptosis through the NLRP3/Caspase-1/GSDMD/IL-1β/IL-18 signaling pathway to reduce the risk of kidney-stone formation.Keywords: pyroptosis, kidney stones, calcium oxalate crystals, selenized polysaccharide