PMID- 34131437 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210617 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 22 IP - 2 DP - 2021 Aug TI - Activation of the NLRC4 inflammasome in renal tubular epithelial cell injury in diabetic nephropathy. PG - 814 LID - 10.3892/etm.2021.10246 [doi] LID - 814 AB - 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-1beta 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-1beta 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. CI - Copyright: (c) Wang et al. FAU - Wang, Yulin AU - Wang Y AD - Department of Nephrology, Zhengzhou University, Zhengzhou, Henan 450000, P.R. China. FAU - Gou, Rong AU - Gou R AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. FAU - Yu, Lu AU - Yu L AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. FAU - Wang, Liuwei AU - Wang L AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. FAU - Yang, Zijun AU - Yang Z AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. FAU - Guo, Yanhong AU - Guo Y AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. FAU - Tang, Lin AU - Tang L AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. LA - eng PT - Journal Article DEP - 20210528 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC8193214 OTO - NOTNLM OT - NLRC4 inflammasome OT - diabetic nephropathy OT - mitophagy OT - renal tubular epithelial cells COIS- The authors declare that they have no competing interests. EDAT- 2021/06/17 06:00 MHDA- 2021/06/17 06:01 PMCR- 2021/05/28 CRDT- 2021/06/16 06:47 PHST- 2020/12/22 00:00 [received] PHST- 2021/05/04 00:00 [accepted] PHST- 2021/06/16 06:47 [entrez] PHST- 2021/06/17 06:00 [pubmed] PHST- 2021/06/17 06:01 [medline] PHST- 2021/05/28 00:00 [pmc-release] AID - ETM-0-0-10246 [pii] AID - 10.3892/etm.2021.10246 [doi] PST - ppublish SO - Exp Ther Med. 2021 Aug;22(2):814. doi: 10.3892/etm.2021.10246. Epub 2021 May 28.