Proximal Tubule Toll-Like Receptor 4 Expression Linked to Inflammation and Apoptosis following Hypoxia/Reoxygenation Injury

Liu, Xiujuan; Yan, Tao; Geng, Yan-Qiu; Wang, Zhen; Ye, Jun-Hong; Yin, Xiu-Ying; Fu, Bo

doi:10.1159/000360549

Cited by 17 publications

(20 citation statements)

References 28 publications

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“…There is growing evidence that inflammation erves a key function in acute kidney injury induced by I/R [2, 3, 20]. Our research demonstrated that Res-DAP5-NP decreased the levels of TNF-α, IL-1β, and IL-6 in renal tissue and represents a feasible method to reduce inflammation-related injury.…”

Section: Discussionmentioning

confidence: 56%

“…Apoptosis and inflammation were reported as crucial mechanisms underlying kidney I/R injury, and thus potential therapeutics against renal injury [2, 3]. …”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis is a vital pathological processes in acute kidney injury induced by I/R [2, 3], which was significantly inhibited by Res-DAP5-NP. In addition, Res-DAP5-NP promoted the expression of p-DAPK and inhibited the expression of p-CaMK and p-AKT in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the precise mechanisms are not well understood. It has been reported that cell apoptosis and inflammation serves a key function in acute kidney injury incuced by I/R [2, 3]. Therefore, inhibiting apoptosis and inflammation may be an effective strategy to attenuate renal I/R injury.…”

Section: Introductionmentioning

confidence: 99%

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Nanoparticle-mediated dual delivery of resveratrol and DAP5 ameliorates kidney ischemia/reperfusion injury by inhibiting cell apoptosis and inflammation

Zhang

Xie

et al. 2017

Oncotarget

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Ischemia reperfusion (I/R) injury is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. NMDA receptor inhibitor (DAP5) and resveratrol (Res) could ameliorate kidney I/R injury, but their use is limited by low aqueous solubility and poor stability. Here, we examined the potential protective effects of Res-DAP5 nanoparticles (NP) against renal I/R injury. Mice were subjected to renal ischemia for 30 min followed by reperfusion for 24 h. The results showed that Res-DAP5-NP could decreased serum creatinine (Cr) and urea nitrogen (BUN), alleviated tubular damage and oxidative stress. In addition, Res-DAP5-NP suppressed cell apoptosis, promoted the expression of p-DAPK, and inhibited the expression of p-CaMK and p-AKT. Furthermore, Res-DAP5-NP decreased the production of pro-inflammatory cytokines such as tumor necrosis factor-α, IL-1β, IL-6, and p-IκBα induced by renal I/R injury. In addition, Res-DAP5-NP also attenuated renal I/R injury in vivo, as manifested by increase in cell viability, SOD level, and the expression of p-DAPK, decreases in intracellular Ca2+ concentration and the expression of p-CaMK. Taken together, our findings indicates that Res-DAP5-NP could effectively protect renal I/R injury by inhibiting apoptosis and inflammation responses, possibly through AKT/NMDA/CaMK/DAPK and NF-κB pathways.

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Section: Discussionmentioning

confidence: 56%

“…Apoptosis and inflammation were reported as crucial mechanisms underlying kidney I/R injury, and thus potential therapeutics against renal injury [2, 3]. …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nanoparticle-mediated dual delivery of resveratrol and DAP5 ameliorates kidney ischemia/reperfusion injury by inhibiting cell apoptosis and inflammation

Zhang

Xie

et al. 2017

Oncotarget

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“…; Liu et al . ); activation of NMDA receptors is associated with increased oxidative stress and renal damage (Pundir et al . ).…”

Section: Discussionmentioning

confidence: 99%

Ketamine suppresses hypoxia‐induced inflammatory responses in the late‐gestation ovine fetal kidney cortex

Chang

Zarate

Rabaglino

et al. 2015

The Journal of Physiology

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Key pointsr The fetus responds to decreases in arterial partial pressure of oxygen by redirecting the blood flow mainly to the brain and the heart, at a cost to other peripheral organs like the kidneys.r Renal hypoxia and ischaemia stimulate inflammatory and apoptotic responses. r Ketamine, an NMDA receptor antagonist, is able to reduce renal immune and inflammatory gene expressions stimulated by hypoxia.r Ketamine may have therapeutic potential for protection against ischaemic renal damage in fetuses subjected to acute hypoxia.Abstract Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischaemia as a consequence of the physiological redistribution of combined ventricular output. Because of the potential ischaemia-reperfusion injury to the kidney, we hypothesized that it would respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-methyl-D-aspartate receptor antagonist) would reduce or block this response. Hypoxia was induced for 30 min in chronically catheterized fetal sheep (125 ± 3 days), with or without ketamine (3 mg kg −1 ) administered intravenously to the fetus 10 min prior to hypoxia. Gene expression in fetal kidney cortex collected 24 h after the onset of hypoxia was analysed using ovine Agilent 15.5k array and validated with qPCR and immunohistochemistry in four groups of ewes: normoxic control, normoxia + ketamine, hypoxic control and hypoxia + ketamine (n = 3-4 per group). Significant differences in gene expression between groups were determined with t-statistics using the limma package for R (P ࣘ 0.05). Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 downregulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the downregulated metabolic responses. We conclude that our transcriptomics modelling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischaemic renal damage.

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The pathogenesis and management of renal scarring in children with vesicoureteric reflux and pyelonephritis

2019

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Proximal Tubule Toll-Like Receptor 4 Expression Linked to Inflammation and Apoptosis following Hypoxia/Reoxygenation Injury

Cited by 17 publications

References 28 publications

Nanoparticle-mediated dual delivery of resveratrol and DAP5 ameliorates kidney ischemia/reperfusion injury by inhibiting cell apoptosis and inflammation

Nanoparticle-mediated dual delivery of resveratrol and DAP5 ameliorates kidney ischemia/reperfusion injury by inhibiting cell apoptosis and inflammation

Ketamine suppresses hypoxia‐induced inflammatory responses in the late‐gestation ovine fetal kidney cortex

The pathogenesis and management of renal scarring in children with vesicoureteric reflux and pyelonephritis

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