Cellular pathophysiology of ischemic acute kidney injury

Bonventre, Joseph V.; Yang, Li

doi:10.1172/jci45161

Cited by 1,639 publications

(1,723 citation statements)

References 147 publications

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“…The first consequence of renal IR is tubular cell death, leading to renal dysfunction and cytokine release. 28 Indeed, we observed that KC and MCP-1 were reduced in WT mice transplanted with Nlrp3KO bone marrow, which also experienced low levels of necrosis. Because Nlrp3 is able to form the Nlrp3 inflammasome and subsequently activate the proinflammatory cytokine IL-1b (canonical pathway), we speculated that a reduction in a proinflammatory response might underlie improved renal function in chimeric mice.…”

Section: Nlrp3 Regulates Renal Repairmentioning

confidence: 75%

A Tissue-Specific Role for Nlrp3 in Tubular Epithelial Repair after Renal Ischemia/Reperfusion

Bakker

Butter

Claessen

et al. 2014

The American Journal of Pathology

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Section: Nlrp3 Regulates Renal Repairmentioning

confidence: 75%

A Tissue-Specific Role for Nlrp3 in Tubular Epithelial Repair after Renal Ischemia/Reperfusion

Bakker

Butter

Claessen

et al. 2014

The American Journal of Pathology

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“…7 Several proinflammatory and chemotactic cytokines regulated by NF-kB, including IL-1b, IL-6, IL-8, and TNF-a are expressed from renal tubular epithelial cells, the targets, and mediators of IR. 25 TNF-a is capable of up-regulating its own expression as well as the expression of other genes pivotal to the inflammatory response. 26 It has been suggested that IR-induced TNF-a expression may result in cell injury via distinct mechanisms such as direct cytotoxicity like induction of dysfunction and/or apoptosis 27 and neutrophil-mediated tissue injury.…”

Section: Discussionmentioning

confidence: 99%

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

et al. 2014

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We investigated the changes in the serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-6, the pro-inflammatory cytokines, and the possible effect of melatonin on the modulation of these inflammatory molecules after renal ischemia reperfusion (IR). The study was carried out in the laboratory of Department of Pharmacology. Forty-six male Wistar albino rats were divided into five groups as control (n ¼ 6), positive control (n ¼ 4), sham (n ¼ 12), renal IR (n ¼ 12), and renal IR melatonin (n ¼ 12). After 1 h renal pedicle occlusion, the blood samples were taken for the measurement of cytokine levels at second hour of the reperfusion. The rats were sacrificed after 24 h of reperfusion for histopathological evaluation. Melatonin or vehicle was administrated to IR rats. Lipopolysaccharide (LPS) was administered to the positive control group and the blood was taken at fourth hour. Serum TNF-a levels increased significantly in renal IR and LPS groups. Serum IL-6 levels were not different from control except the LPS group. There was no significant correlation between the serum TNF-a levels and the histopathological score after renal IR. Melatonin treatment reversed the increase of serum TNF-a levels and histopathological injury in renal tissue after renal IR. Melatonin may have a protective effect by reducing the serum level of TNF-a in renal IR.

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“…From 5% to 7% of hospitalized patients are reported to experience AKI (2,3); the estimated annual health care expenditures attributable to hospital-acquired AKI exceed $10 billion (4). Renal ischemia reperfusion injury (IRI) associated with renal transplantation, postcardiopulmonary bypass surgeries, and other major vascular surgeries is the leading cause of AKI; sepsis and nephrotoxic drug injury are other major contributory factors (5,6). The physiological and cellular hallmarks of IRI are the loss of renal function, vasoconstriction, cell death within the renal tubular epithelium, and initiation of an inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Cell-specific translational profiling in acute kidney injury

et al. 2014

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Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results in substantial morbidity and mortality. Considerable effort has gone toward identification of diagnostic biomarkers and analysis of AKI-associated molecular events; however, most studies have adopted organ-wide approaches and have not elucidated the interplay among different cell types involved in AKI pathophysiology. To better characterize AKI-associated molecular and cellular events, we developed a mouse line that enables the identification of translational profiles in specific cell types. This strategy relies on CRE recombinase-dependent activation of an EGFP-tagged L10a ribosomal protein subunit, which allows translating ribosome affinity purification (TRAP) of mRNA populations in CRE-expressing cells. Combining this mouse line with cell type-specific CRE-driver lines, we identified distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI, distinct translational signatures were identified in the nephron, kidney interstitial cell populations, vascular endothelium, and macrophages/monocytes. Furthermore, TRAP captured known IRI-associated markers, validating this approach. Biological function annotation, canonical pathway analysis, and in situ analysis of identified response genes provided insight into cell-specific injury signatures. Our study provides a deep, cell-based view of early injury-associated molecular events in AKI and documents a versatile, genetic tool to monitor cell-specific and temporal-specific biological processes in disease modeling.

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Cellular pathophysiology of ischemic acute kidney injury

Cited by 1,639 publications

References 147 publications

A Tissue-Specific Role for Nlrp3 in Tubular Epithelial Repair after Renal Ischemia/Reperfusion

A Tissue-Specific Role for Nlrp3 in Tubular Epithelial Repair after Renal Ischemia/Reperfusion

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

Cell-specific translational profiling in acute kidney injury

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