Metadherin silencing results in the inhibition of pyroptosis in lipopolysaccharide/adenosine triphosphate - stimulated renal tubular epithelial cells.

Abstract

Pyroptosis is induced following inflammation via activation of the NLRP3 inflammasome. Lipopolysaccharide (LPS)-induced acute inflammation causes pyroptosis in renal tubular epithelial cells, which aggravates kidney damage and is involved in physiopathological processes in multiple renal diseases. Metadherin (Mtdh) induces inflammation by NLRP3 inflammasome activation. Specifically, it induces inflammatory injury in the kidney by activating the nuclear factor kappa B (NF-κB) signaling pathway, which is involved in NLRP3 inflammasome activation. However, the role of Mtdh in pyroptosis in renal tubular epithelial cells is unclear. Therefore, we investigated whether Mtdh participates in pyroptosis in LPS/adenosine triphosphate (ATP)-treated NRK-52E cells by activating the NLRP3 inflammasome and NF-κB signaling pathway. We induced pyroptosis in NRK-52E cells with LPS/ATP, after which Mtdh was silenced via transfection with small interfering RNA. LPS/ATP upregulated Mtdh expression and induced pyroptosis and NLRP3 inflammasome activation in NRK-52E cells. However, downregulation of Mtdh expression resulted in the alleviation of pyroptosis in LPS/ATP-treated NRK-52E cells. Additionally, activation of the NLRP3 inflammasome and NF-κB signaling pathway was inhibited. This demonstrates that downregulation of Mtdh expression results in the inhibition of pyroptosis in LPS/ATP-treated NRK-52E cells through the suppression of NLRP3 inflammasome activation, which occurs via inhibition of the NF-κB signaling pathway.

• Authors: Xiuping Duan, Yashan Song, Fuji Li, Yunhua Liao, Wenting Liu
• Journal: Tissue & cell (Tissue Cell) Vol. 75 Pg. 101722 (Apr 2022) ISSN: 1532-3072 [Electronic] Scotland
• PMID: 35026615 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Lipopolysaccharides
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Epithelial Cells (metabolism)
• Lipopolysaccharides (toxicity)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Pyroptosis (genetics)