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13 April 2019 : Laboratory Research  

The Overexpression of Sirtuin1 (SIRT1) Alleviated Lipopolysaccharide (LPS)-Induced Acute Kidney Injury (AKI) via Inhibiting the Activation of Nucleotide-Binding Oligomerization Domain-Like Receptors (NLR) Family Pyrin Domain Containing 3 (NLRP3) Inflammasome

Qiufang Gao1ACEF, Hengting Zhu1ABDE*

DOI: 10.12659/MSM.913146

Med Sci Monit 2019; 25:2718-2726

Abstract

BACKGROUND: Sepsis-induced acute kidney injury (AKI) is threatening the patients with sepsis, and nucleotide-binding oligomerization domain-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is considered to play a critical role in this complication of sepsis and might be regulated by sirtuin1 (SIRT1). Thus, we explored the roles of NLRP3 and SIRT1 in the lipopolysaccharide (LPS)-induced AKI in the HK-2 cell line.

MATERIAL AND METHODS: Cell viability was assessed by Cell Counting Kit-8 (CCK-8). Apoptosis rate was measured by flow cytometry. Protein levels of interleukin (IL)-1β and IL-18 were tested by enzyme-linked immunosorbent assay (ELISA) and NLRP3, cleaved caspase-1, caspase-1 were tested by western blot. The mRNA levels of IL-1β, IL-18, and SIRT1 were quantified by qPCR.

RESULTS: LPS could decrease cell viability and the expression of SIRT1 and elevate the expressions of IL-1β, IL-18, NLRP,3 and cleaved caspase-1. However, the overexpression of SIRT1 could upregulate cell viability and expression of caspase-1 and downregulate apoptosis rate, expressions of NLRP3, IL-1β, IL-18, and cleaved caspase-1.

CONCLUSIONS: NLRP3 inflammasome could act as a critical regulator promoting the process of AKI induced by LPS, and the overexpression of SIRT1 might be able to suppress the activation of NLRP3 and therefore resist the kidney injury, showing promise to be used as a target in the treatment of sepsis-induced AKI.

Keywords: Acute Kidney Injury, Gene Expression Regulation, Archaeal, Inflammasomes, Lipopolysaccharides, Sirtuin 1, Caspase 1, Cell Line, Interleukin-18, Kidney, NLR Family, Pyrin Domain-Containing 3 Protein, Pyrin Domain, Sepsis

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750