Activation of the NLRC4 inflammasome in renal tubular epithelial cell injury in diabetic nephropathy

Wang,Yulin; Gou,Rong; Yu,Lu; Wang,Liuwei; Yang,Zijun; Guo,Yanhong; Tang,Lin

doi:10.3892/etm.2021.10246

Activation of the NLRC4 inflammasome in renal tubular epithelial cell injury in diabetic nephropathy

Authors:
- Yulin Wang
- Rong Gou
- Lu Yu
- Liuwei Wang
- Zijun Yang
- Yanhong Guo
- Lin Tang
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Affiliations: Department of Nephrology, Zhengzhou University, Zhengzhou, Henan 450000, P.R. China, Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: May 28, 2021 https://doi.org/10.3892/etm.2021.10246
Article Number: 814
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal tubular interstitial injury plays a key role in the progression of diabetic nephropathy (DN) and, thus, the study of renal tubular injury in DN is important. The aim of the present study was to elucidate the role of the NLR family CARD domain containing 4 (NLRC4) inflammasome in renal tubular epithelial cell (RTEC) injury in DN. Human kidney biopsy tissues were obtained from patients with DN, and normal kidney tissues were obtained from nephrectomies performed for renal hamartoma. Human RTECs (HK2 cells) were divided into normal glucose (D‑glucose 5.6 mmol/l), high glucose (HG; 30 mmol/l), high osmotic (D‑glucose 5.6 mmol/l + D‑mannitol 24.4 mmol/l), HG + NLRC4 small interfering (si)RNA or HG + siRNA control groups. Then, the expression levels of NLRC4, PTEN‑induced kinase 1 (PINK1) and parkin, as well as the levels of mitochondrial reactive oxygen species, which are associated with mitophagy, were observed. The expression levels of NLRC4, PINK1, parkin and phosphorylated parkin in the RTECs of patients with DN were higher compared with those in normal controls. In HK2 cells, HG stimulated the expression of NLRC4, the secretion of IL‑1β and IL‑18 and cell death. Moreover, knockdown of NLRC4 expression in HK2 cells treated with HG reduced the secretion of the inflammatory cytokines, IL‑1β and IL‑18. The findings of the present study may provide a rationale for the development of treatments for patients with DN by preventing inflammasome activation.

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