Open Access

Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signaling in vitro and in vivo

  • Authors:
    • Yue Chen
    • Shushuai Yang
    • Hailong Kong
    • Qi Wang
    • Shiqun Chen
    • Xingyu Wang
    • Liqun Chen
    • Shiyong Qi
  • View Affiliations

  • Published online on: September 20, 2023     https://doi.org/10.3892/mmr.2023.13096
  • Article Number: 209
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Calcium oxalate kidney stone has become an urgent issue due to its high incidence and recurrence rate. Thus, it is necessary to explore for mechanisms of calcium oxalate stones formation. Previous studies demonstrated that oxalate crystals could induce the activation of nucleotide‑binding domain and leucine‑rich repeat‑containing family pyrin domain‑containing 3 (NLRP3) inflammasome and change the renal tubular epithelium adhesion. However, the type and molecular mechanism of NLRP3 inflammasome‑mediated calcium oxalate stones formation still need to be further investigated. In the present study, it was confirmed that the NLRP3‑gasdermin D (GSDMD) signaling was involved in oxalate‑induced cell injury in vitro and in vivo. Inhibition of reactive oxygen species production could effectively prevent the NLRP3 inflammasome formation in oxalate‑treated HK‑2 cells. NLRP3 gene silence could inhibit the DNA damage and cellular membrane injury of HK‑2 cells treated with oxalate. The ultrastructural changes of several organelles and particular structures, similar to typical cell pyroptosis, were observed in oxalate‑stimulated HK‑2 cells. NLRP3 gene silence could antagonize the oxalate‑induced injury and ultrastructure changes. Additionally, NSA (GSDMD inhibitor) could prevent the oxalate‑induced injury of membrane integrity in HK‑2 cells. Moreover, oxalate crystals were significantly decreased in GSDMD‑/‑ mice compared with wild‑type mice with glyoxylic acid. Together, NLRP3‑GSDMD pathway was involved in the oxalate‑induced pyroptotic injury in HK‑2 cells. GSDMD and its cleavage form GSDMD‑N played an important role in the oxalate‑induced renal cell injury and oxalate calcium crystals formation in vitro and in vivo. This provided a new target for prevention and treatment of oxalate nephropathy and oxalate calcium stones.
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November-2023
Volume 28 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Chen Y, Yang S, Kong H, Wang Q, Chen S, Wang X, Chen L and Qi S: Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signaling <em>in vitro</em> and <em>in vivo</em>. Mol Med Rep 28: 209, 2023.
APA
Chen, Y., Yang, S., Kong, H., Wang, Q., Chen, S., Wang, X. ... Qi, S. (2023). Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signaling <em>in vitro</em> and <em>in vivo</em>. Molecular Medicine Reports, 28, 209. https://doi.org/10.3892/mmr.2023.13096
MLA
Chen, Y., Yang, S., Kong, H., Wang, Q., Chen, S., Wang, X., Chen, L., Qi, S."Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signaling <em>in vitro</em> and <em>in vivo</em>". Molecular Medicine Reports 28.5 (2023): 209.
Chicago
Chen, Y., Yang, S., Kong, H., Wang, Q., Chen, S., Wang, X., Chen, L., Qi, S."Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signaling <em>in vitro</em> and <em>in vivo</em>". Molecular Medicine Reports 28, no. 5 (2023): 209. https://doi.org/10.3892/mmr.2023.13096