Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Park, Sang Won; Chen, Sean W. C.; Kim, Mihwa; D’Agati, Vivette D.; Lee, H Thomas

doi:10.1038/labinvest.2009.143

Cited by 17 publications

(19 citation statements)

References 53 publications

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“…However, a previous study suggested that a systemic increase of HSP27, instead of a local increase, in transgenic mice counteracts this protection by exacerbating renal and systemic inflammation (36). HSP27 has been shown to inhibit the disassociation of actin and microfibrils, offering protection and stabilization to the cytoskeleton (34,35). This function of HSP27 is important in the tolerance of individual cells and organs to different stresses by maintaining the integrity of the endothelium and epithelium.…”

Section: Discussionmentioning

confidence: 99%

Ischemic postconditioning prevents renal ischemia reperfusion injury through the induction of heat shock proteins in rats

Guo

Zhao

et al. 2014

Molecular Medicine Reports

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Ischemic postconditioning (IPo) attenuates ischemia-reperfusion injuries (IRI) in various organs, of both animals and humans. This study tested the hypothesis that IPo attenuates renal IRI through the upregulation of heat shock protein (HSP)70, HSP27 and heme oxygenase-1 (HO-1, also known as HSP 32) expression. Adult Sprague Dawley rats were subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h. One group of rats received IPo prior to restoring full perfusion. Another group was administered 100 mg/kg HSP inhibitor quercetin, injected intraperitoneally 1 h prior to ischemia. Control rats received sham operations. Renal IR resulted in severe morphological and pathological changes, with increased serum creatinine and blood urea nitrogen concentrations. IR resulted in increased inflammation by inducing plasma tumor necrosis factor-α and renal nuclear factor kappa-light-chain-enhancer of activated B cells expression. IR also increased lipid peroxidation, as indicated by elevated malondialdehyde content, reduced superoxide dismutase activity and increased renal apoptosis. Renal HSP70, HSP27 and HO-1 mRNA and protein levels were increased by IR and further elevated by IPo. IPo attenuated these changes observed in pathology, lipid peroxidation, apoptosis and inflammation. Quercetin treatment abolished all the protective effects of IPo. In conclusion, this study showed that IPo can attenuate lipid peroxidation, apoptosis and inflammation as well as renal IRI by upregulating the expression of HSP70, HSP27 and HO-1.

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Section: Discussionmentioning

confidence: 99%

Ischemic postconditioning prevents renal ischemia reperfusion injury through the induction of heat shock proteins in rats

Guo

Zhao

et al. 2014

Molecular Medicine Reports

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“…Ozone oxidative preconditioning is mediated by A 1 receptors in a rat model of liver ischemia-reperfusion (León Fernández et al, 2008). Selective intrarenal human A 1 receptor overexpression reduced acute liver (and kidney) injury after hepatic ischemia-reperfusion in mice (Park et al, 2010b). It is claimed that ischemic preconditioning promotes liver regeneration via A 2 receptors on Kupffer cells (Arai et al, 2007).…”

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…A 1 AR activation protects against AKI and also reduces liver and intestinal injury after renal IR injury [62]. We recently demonstrated that severe hepatic IR causes AKI with rapid renal endothelial apoptosis and leukocyte infiltration [63,64]. Endogenous and exogenous activation of renal A 1 ARs protect against liver and kidney injury after in vivo liver IR via pathways involving Akt activation [62,63].…”

Section: Remote Organ Injury Induced Aki Aki-induced Extrarenal Injumentioning

confidence: 99%

“…We recently demonstrated that severe hepatic IR causes AKI with rapid renal endothelial apoptosis and leukocyte infiltration [63,64]. Endogenous and exogenous activation of renal A 1 ARs protect against liver and kidney injury after in vivo liver IR via pathways involving Akt activation [62,63]. Therefore, protecting the kidney reduces liver IR injury and selective overexpression of cytoprotective A 1 ARs in the kidney leads to protection of both liver and kidney after hepatic IR.…”

Section: Remote Organ Injury Induced Aki Aki-induced Extrarenal Injumentioning

confidence: 99%

Adenosine and protection from acute kidney injury

Yap

Lee

2012

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of Review Acute Kidney Injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality, and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor (AR) manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal AR biology and potential clinical therapies for AKI. Recent Findings The 4 AR subtypes (A1AR, A2AAR, A2BAR and A3AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific AR subtype activation needed to produce renal protection. The A1AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion (IR) injury by modulating metabolic demand, decreasing necrosis, apoptosis and inflammation. The A2AAR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation whereas the A2BAR activation protects by direct activation of renal parenchymal ARs. In contrast, the A1AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A3AR-activation exacerbates apoptosis and tissue damage due to renal IR, selective A3AR antagonism may hold promise to attenuate renal IR injury. Finally, renal A1AR activation also protects against renal endothelial dysfunction caused by hepatic IR injury. Summary Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal ARs holds promise in treating AKI and extrarenal injury.

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Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Cited by 17 publications

References 53 publications

Ischemic postconditioning prevents renal ischemia reperfusion injury through the induction of heat shock proteins in rats

Ischemic postconditioning prevents renal ischemia reperfusion injury through the induction of heat shock proteins in rats

Purinergic Signaling and Blood Vessels in Health and Disease

Adenosine and protection from acute kidney injury

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