AUTHOR=Liu Yinghong , He Mingyue , Xiong Hao , Yuan Fang TITLE=Induction of Pyroptosis in Renal Tubular Epithelial Cells Using High Glucose JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.874916 DOI=10.3389/fmed.2022.874916 ISSN=2296-858X ABSTRACT=Background

The micro-inflammatory state is important for the occurrence of diabetic kidney disease (DKD). Here, we aimed to explore the expression of pyroptosis related indicators and ultrastructural characteristics in DKD, and investigate pyroptosis in renal tubular epithelial cells induced by high glucose.

Methods

Immunohistochemistry was used to detect expression of the inflammation-related protein NOD-like receptor protein 3 (NLRP3) and pyroptosis key protein gasdermin D (GSDMD) in kidney tissues of DKD patients. HK-2 cells were cultured in vitro and stimulated with different concentrations of glucose. The changes in HK-2 cell ultrastructure were observed using electronmicroscopy, and western blot was used to detect NLRP3, caspase-1 p20, GSDMD-N, interleukin (IL)-1β, and IL-18 expression.

Results

NLRP3 and GSDMD expression in kidney tissues of DKD patients was higher than that in control subjects. Further, GSDMD expression was positively correlated with that of NLRP3 (r = 0.847, P = 0.02). After stimulating HK-2 cells for 24 h with different glucose concentrations, compared with the control group, the 15 and 30 mmol/L glucose groups showed typical ultrastructural changes of pyroptosis. The protein expression of NLRP3, caspase-1 p20, GSDMD-N, IL-1β, and IL-18 expression in high glucose group increased significantly compared with the control group, and was glucose-concentration-dependent.

Conclusion

High glucose can activate inflammasome, cause inflammatory cytokines release, and induce pyroptosis in HK-2 cells. NLRP3-caspase-1 may be involved in GSDMD-mediated pyroptosis. This study shows a novel relationship between glucose concentration and pyroptosis, which can be studied further to design better therapies for patients with DKD.