Comparison of Endoplasmic Reticulum Stress and Pyroptosis Induced by Pathogenic Calcium Oxalate Monohydrate and Physiologic Calcium Oxalate Dihydrate Crystals in HK-2 Cells: Insights into Kidney Stone Formation

Endoplasmic reticulum stress (ERS) can activate pyroptosis through CHOP and TXNIP; however, the correlation between this process and the formation of kidney stones has not been reported. The purpose is to investigate the effects of calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) on ERS and pyroptosis in HK-2 cells and to explore the formation mechanism of calcium oxalate stones. HK-2 cells were injured by 3 μm COM and COD. COM and COD significantly upregulated the expression levels of GRP78, CHOP, TXNIP, and pyroptosis-related proteins (NLRP3, caspase-1, GSDMD-N, and IL-1β). Fluorescence colocalization revealed that COM induced pyroptosis by inducing the interaction between TXNIP and NLRP3. Both COM and COD crystals can induce ERS and pyroptosis in HK-2 cells. COM induces the interaction with NLRP3 by the upregulation of CHOP and TXNIP and then promotes pyroptosis, while COD only promotes pyroptosis by the upregulation of CHOP. The cytotoxicity and the ability of COM to promote crystal adhesion and aggregation are higher than COD, suggesting that COM is more dangerous for calcium oxalate kidney stone formation.