LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1

Yoo, Joon; Ryong, Dae; Kim, Borim; An, Eun Jung; Lee, Sae-Rom; Joo, Jin; Kang, Young Sun; Ghee, Jung Yeon; Han, Jee‐Young; Bae, Yun Soo

doi:10.1016/j.celrep.2020.108245

Cited by 68 publications

(66 citation statements)

References 51 publications

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“…The antioxidant enzyme HO-1 also plays an important role in LPS-induced renal injury [23,24]. Here, we observed that LPS-injected mice exhibited increased expression of NOX4 in the kidneys, which is consistent with previous studies [21,22]. In addition, HO-1 expression was also increased in LPS-injected mice compared to control mice.…”

Section: Discussionsupporting

confidence: 92%

“…Molecules 2020, 25, x FOR PEER REVIEW 5 of 14 (GSH)/oxidized glutathione (GSSG) ratio, an indicator of oxidative stress, was decreased in the kidneys of LPS-injected mice, which was significantly reversed by apamin ( Figure 5D). Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) produces reactive oxygen species (ROS) and contributes to LPS-induced oxidative stress in the kidney [21,22]. In addition to the pro-oxidant enzyme NOX4, heme oxygenase-1 (HO-1) also plays an important role as a stress-inducible antioxidant enzyme in oxidative stress caused by LPS [23,24].…”

Section: Apamin Suppressed Lps-induced Oxidative Stressmentioning

confidence: 99%

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Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

2020

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Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

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Section: Discussionsupporting

confidence: 92%

Section: Apamin Suppressed Lps-induced Oxidative Stressmentioning

confidence: 99%

Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

2020

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“…However, in obesity-caused renal vascular endothelial damage, O 2 − produced by NOX2 plays a more important role (150). In mouse renal TECs, Yoo et al (151) confirmed that LPS stimulation led to enhanced interaction between SH3YL1 and the anchoring protein P22phox of NOX4, thereby further activating NOX4 and leading to oxidative damage in the cells. In a CLP-induced AKI model, Angara Sureshbabu et al (128) found that necroptosis was activated in kidney cells, and co-immunoprecipitation (co-IP) demonstrated that RIPK3 could directly bind and stabilize NOX4, independent of its downstream signal, MLKL.…”

Section: Mitochondria and Oxidative Stress/nitrosative Stressmentioning

confidence: 98%

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

Wang

et al. 2021

Front. Med.

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Sepsis is a systemic inflammatory response syndrome caused by infection, following with acute injury to multiple organs. Sepsis-induced acute kidney injury (AKI) is currently recognized as one of the most severe complications related to sepsis. The pathophysiology of sepsis-AKI involves multiple cell types, including macrophages, vascular endothelial cells (ECs) and renal tubular epithelial cells (TECs), etc. More significantly, programmed cell death including apoptosis, necroptosis and pyroptosis could be triggered by sepsis in these types of cells, which enhances AKI progress. Moreover, the cross-talk and connections between these cells and cell death are critical for better understanding the pathophysiological basis of sepsis-AKI. Mitochondria dysfunction and oxidative stress are traditionally considered as the leading triggers of programmed cell death. Recent findings also highlight that autophagy, mitochondria quality control and epigenetic modification, which interact with programmed cell death, participate in the damage process in sepsis-AKI. The insightful understanding of the programmed cell death in sepsis-AKI could facilitate the development of effective treatment, as well as preventive methods.

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“…NADPH oxidases are a major source of reactive oxygen species (ROS) in the kidney in normal and pathological conditions (Sedeek et al 2013). Among NADPH oxidase isoforms, NADPH oxidase4 (NOX4), which regulates oxidative stress, is highly expressed in the kidney and has an important role in kidney diseases (Yoo et al 2020). We previously found that NOX4 aggravated kidney injury by promoting ROS-mediated programmed cell death and in ammation (Wang, Yang 2020b, Meng et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Macrophages-Derived, LRG1-Enriched Extracellular Vesicles Exacerbate Aristolochic Acid Nephropathy Via A TGFβR1-Dependent Manner

Jiang

Dong

et al. 2021

Preprint

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Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some herbal medicines, but treatment remains ineffective. We previously found NADPH oxidases 4 (NOX4), which regulates oxidative stress, play an important role in kidney injury model. However, its regulatory mechanism of action in AAN is still obscure. In this study, we established AAN model in vivo, a co-culture system of macrophage and TEC, and macrophage/TEC conditioned media culture model in vitro respectively. We found macrophages infiltration promoted injury，oxidative stress and apoptosis of TEC. Furthermore, the role of macrophage in AAN was dependent on macrophages-derived EV. Importantly, we found that macrophages-derived, Leucine-rich α-2-glycoprotein 1(LRG1)-enriched EV induced TEC injury and apoptosis of via a TGFβR1-dependent process. Mechanistically, macrophages-derived, LRG1-enriched EV mediating TECs injury by upregulating NOX4 in AAN model. This study may help design a better therapeutic strategy to treat AAN patients.

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LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1

Abstract: Highlights d H 2 O 2 generation is mediated by interaction of Nox4 with p22 phox -SH3YL1 d SH3YL1-Nox4 regulates pro-inflammatory cytokine production and tubular damage d SH3YL1-Nox4 complex plays an important role in LPSinduced acute kidney injury

Cited by 68 publications

References 51 publications

Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

Macrophages-Derived, LRG1-Enriched Extracellular Vesicles Exacerbate Aristolochic Acid Nephropathy Via A TGFβR1-Dependent Manner

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