Acute Kidney Injury and Sepsis

Skube, Steven J.; Katz, Stephen A.; Chipman, Jeffrey G.; Tignanelli, Christopher J.

doi:10.1089/sur.2017.261

Cited by 76 publications

(51 citation statements)

References 80 publications

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“…Ischemia and subsequent reperfusion injury usually occur when the blood flow is blocked during surgeries or severe diseases. For the kidney, cardiac dysregulations and surgical interventions, such as kidney transplantation or nephron-sparing surgery, are the leading causes of RIRI ( Venkatachalam et al, 2015 ; Skube et al, 2018 ). This lesion results in AKI and presents the fundamental problems and even contributes to a high morbidity and mortality rate ( Chawla et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNA-374b-5p From Tubular Epithelial Cells Promoted M1 Macrophages Activation and Worsened Renal Ischemia/Reperfusion Injury

Ding

Zheng

Wang

et al. 2020

Front. Cell Dev. Biol.

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Tubular epithelial cells (TECs) represent the primary site of renal ischemia/reperfusion injury (RIRI). However, whether the damage of TECs could drive the initiation of inflammation was unclear. Here we investigated the role of the TECs and macrophages during RIRI. Increased expression of inflammation response and activated M1 macrophage were determined in the mice model of RIRI. Moreover, we demonstrated global miRNA expression profiling of renal exosomes, and miR-374b-5p was most upregulated in these exosomes in vivo. Inhibition of miR-374b-5p in the mice upon RIR operation would alleviate the kidney injury via decreasing the production of proinflammatory cytokines and suppressing the macrophage activation. Similar results were also identified in the hypoxia-induced cell model where exosomal miR-374b-5p was dramatically upregulated. Uptake of exosomes derived from the hypoxic TECs by macrophages would trigger M1 polarization via transferring miR-374b-5p. Besides, we confirmed that miR-374b-5p could directly bind to Socs1 using a dual-luciferase reporter assay. Notably, when we injected the miR-374b-5p-enriched exosomes into mice, a high-level inflammatory response and M1 macrophage activation were performed. Our studies demonstrated that exosomal miR-374b-5p played an essential role in the communication between injured TECs and macrophages, resulting in the M1 macrophage activation during RIRI. The blockage of the release of such exosomes may serve as a new therapeutic strategy for RIRI.

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Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNA-374b-5p From Tubular Epithelial Cells Promoted M1 Macrophages Activation and Worsened Renal Ischemia/Reperfusion Injury

Ding

Zheng

Wang

et al. 2020

Front. Cell Dev. Biol.

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“…Sepsis is a severe condition characterized by systemic inflammatory response syndrome and the presence of infection that has fatal consequences, including acute kidney injury (AKI) [1]. There is a very strong evidence that sepsis and septic shock are the most common causes of AKI in critically ill patients, accounting for more than 50% of AKI cases in the intensive care unit (ICU) [2].…”

Section: Introductionmentioning

confidence: 99%

CXCL14 Overexpression Attenuates Sepsis-Associated Acute Kidney Injury by Inhibiting Proinflammatory Cytokine Production

Gan

et al. 2020

Mediators of Inflammation

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CXCL14 is a relatively novel chemokine with a wide spectrum of biological activities. The present study was designed to investigate whether CXCL14 overexpression attenuates sepsis-associated acute kidney injury (AKI) in mice. Sepsis model has been established by cecal ligation and puncture (CLP). CLP induced AKI in mice as assessed by increased renal neutrophil gelatinase-associated lipocalin (NGAL) expression and serum creatinine levels. We found that renal CXCL14 expression in the kidney was significantly decreased at 12 hours after CLP. Correlation analysis demonstrated a negative association between renal CXCL14 expression and AKI markers including serum creatinine and renal NGAL. Moreover, CXCL14 overexpression reduced cytokine (TNF-α, IL-6, and IL-1β) production and NGAL expression in the kidney and decreased serum creatinine levels. In vivo and in vitro experiments found that CXCL14 overexpression inhibited M1 macrophage polarization but increased M2 polarization. Together, these results suggest that CXCL14 overexpression attenuates sepsis-associated AKI probably through the downregulation of macrophages-derived cytokine production. However, further studies are required to elucidate the underlying mechanism.

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“…AKI is accompanied by severe inflammatory reactions that can lead to kidney damage and declines in renal function [25]. The NF-κB and MAPK pathways play an important role in mediating the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Phillyrin Relieves Lipopolysaccharide-Induced AKI by Protecting Against Glycocalyx Damage and Inhibiting Inflammatory Responses

Zhang

et al. 2019

Inflammation

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Damage to the integrity of heparin sulfate (HS) in the endothelial glycocalyx is an important factor of glomerular filtration barrier dysfunction, which is the basic pathological feature of acute kidney injury (AKI). AKI is a common clinical critical illness with few drugs options offering effective treatment. Phillyrin (Phil), the main pharmacological component of Forsythia suspensa, possesses a wide range of pharmacological activities. However, the effects of Phil on lipopolysaccharide (LPS)-induced AKI have yet to be reported. The aim of the present study is to analyze the effects of Phil on HS damage and inflammatory signaling pathways in LPS-induced AKI. Results revealed that Phil reduces pathological changes and improves renal function in LPS-induced AKI. Further analysis indicated that Phil effectively protects against glycocalyx HS degradation in LPS-stimulated EA.hy926 cells in vitro and LPS-induced AKI mice in vivo. The protective effect of Phil on HS damage may be associated with the isolate's ability to suppress the production of reactive oxygen species, and decrease expression levels of cathepsin L and heparanase in vitro and in vivo. In addition, ELISA and Western blot results revealed that Phil inhibits the activation of the NF-κB and MAPK signaling pathways and decreases the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-induced ARDS mice. In general, protection against endothelial glycocalyx HS damage and inhibition of inflammatory responses by Phil may be used as treatment targets for LPS-induced AKI.

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Acute Kidney Injury and Sepsis

Abstract: In patients with sepsis-associated AKI, appropriate fluid resuscitation and maintenance of blood pressure are important to prevent further kidney damage. Despite multiple clinical trials, the mechanisms of sepsis-associated AKI and the best treatment options remain unclear.

Cited by 76 publications

References 80 publications

Exosomal MicroRNA-374b-5p From Tubular Epithelial Cells Promoted M1 Macrophages Activation and Worsened Renal Ischemia/Reperfusion Injury

Exosomal MicroRNA-374b-5p From Tubular Epithelial Cells Promoted M1 Macrophages Activation and Worsened Renal Ischemia/Reperfusion Injury

CXCL14 Overexpression Attenuates Sepsis-Associated Acute Kidney Injury by Inhibiting Proinflammatory Cytokine Production

Phillyrin Relieves Lipopolysaccharide-Induced AKI by Protecting Against Glycocalyx Damage and Inhibiting Inflammatory Responses

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