Limb ischemic preconditioning protects against contrast-induced acute kidney injury in rats via phosphorylation of GSK-3β

Liu, Tongqiang; Fang, Yi; Liu, Shaopeng; Lei, Yu; Zhang, Hui; Liang, Mingyu; Ding, Xiaoqiang

doi:10.1016/j.freeradbiomed.2014.10.509

Cited by 44 publications

(45 citation statements)

References 65 publications

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“…Moreover, the limb IPC–induced kidney protection was found to be associated with inhibitory phosphorylation of the signaling transducer GSK3β, which is downstream of the PI3K/Akt signaling pathway. Inhibition of GSK3β by SB216763, a selective small molecule inhibitor, mimicked the kidney protective effect of limb IPC and likewise attenuated loss of kidney function and prevented the acute kidney histological injury elicited by iohexol 42 .…”

Section: Recent Advancesmentioning

confidence: 95%

“…To understand the mechanism of action responsible for kidney protection elicited by remote IPC, Liu et al 42 dissected the RISK signaling cascades 43,44 . Rats with preexisting CKD caused by partial nephrectomy were subjected to limb IPC prior to iohexol-induced AKI.…”

Section: Recent Advancesmentioning

confidence: 99%

“…Rats with preexisting CKD caused by partial nephrectomy were subjected to limb IPC prior to iohexol-induced AKI. The limb IPC–induced kidney protection could be abrogated by pretreatment with wortmannin (a specific inhibitor of PI3K) but not by U0126 (a ERK1/2 inhibitor) 42 . This observation was confirmed using another selective inhibitor of PI3K, LY294002, and another ERK1/2 inhibitor, PD98059.…”

Section: Recent Advancesmentioning

confidence: 99%

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Remote Ischemic Preconditioning for Kidney Protection: GSK3β-Centric Insights Into the Mechanism of Action

Liu

Gong

2015

American Journal of Kidney Diseases

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Preventing acute kidney injury (AKI) in high-risk patients following medical interventions is a paramount challenge for clinical practice. Recent data from animal experiments and clinical trials indicate that remote ischemic preconditioning (IPC), represented by limb IPC, confers a protective action on the kidney. IPC is effective in reducing the risk of AKI following cardiovascular interventions and the use of iodinated radiocontrast media. Nevertheless, the underlying mechanisms for this protective effect remain elusive. A protective signal is conveyed from the remote site undergoing IPC, like the limb, to target organs, like the kidney, via multiple potential communication pathways, which may involve a humoral, neuronal, and systemic mechanisms. Diverse transmitting pathways trigger a variety of signaling cascades, including the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, all of which converge on glycogen synthase kinase (GSK)3β. Inhibition of GSK3β subsequent to IPC reinforces the Nrf2-mediated antioxidant defense, diminishes the NFκB-dependent pro-inflammatory response, and exerts prosurvival effects ensuing from the desensitized mitochondria permeability transition. Thus, therapeutic targeting of GSK3β by IPC or by pharmacologic preconditioning with existing FDA-approved drugs having GSK3β inhibitory activities might represent a pragmatic and cost-effective adjuvant strategy for kidney protection and prophylaxis against AKI.

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Section: Recent Advancesmentioning

confidence: 95%

Section: Recent Advancesmentioning

confidence: 99%

Section: Recent Advancesmentioning

confidence: 99%

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Remote Ischemic Preconditioning for Kidney Protection: GSK3β-Centric Insights Into the Mechanism of Action

Liu

Gong

2015

American Journal of Kidney Diseases

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“…Thus, CKD rodent models plus iv. RCM injection is also used to model CI-AKI [82, 84, 85, 175]. For example, RCM induces tubular necrosis in diabetic nephropathy kidneys (Figures 4(l) and 4(m)) [37].…”

Section: Further Histological Changes Related Primarily To the Modmentioning

confidence: 99%

Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

Kiss

Hamar

2016

BioMed Research International

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Contrast-induced acute kidney injury (CI-AKI) can occur in 3–25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments.

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“…Inflammation and peripheral immune responses secondary to ischemic kidney injury have gained general acceptance from various clinical and experimental studies [12,23,24]. CD4 + CD25 + Foxp3 + Tregs were immunosuppressive T-cell subsets in vivo via anergy response to specific antigens and antigen-presenting cells, as well as suppressive response to the activation and proliferation of CD4 + and CD8 + lymphocytes [25].…”

Section: Discussionmentioning

confidence: 99%

Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

Liang

Kuang

et al. 2017

Am J Nephrol

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Background: Regulatory T (Treg) cells are a highly suppressive subset of CD4⁺ lymphocytes and have recently been proved to be crucial to suppress the inflammatory responses of ischemic kidney injury. CD28 superagonists (CD28sa) are monoclonal antibodies that preferentially expand Treg cells without a T-cell receptor and a costimulatory signal. This study aims to test the protection and discover the mechanisms of CD28sa treatment against renal ischemia-reperfusion (IR) injury (IRI). Methods: Male C57BL/6N mice were treated with CD28sa via peritoneal injection (0.1 mg) 6 days before the induction of IRI, or with 18-min ischemic precondition (IPC). IRI was induced by bilateral clamping of renal pedicles for 35 min followed by reperfusion. The role of Treg expansion in renal protection conferred by CD28sa treatment was examined using anti-CD25 antibody. Results: CD28sa treatment alone significantly increased the percentage of Treg cells in the spleen (18.10 ± 2.00 vs. 6.64 ± 0.86%, p < 0.01), peripheral blood (16.43 ± 5.94 vs. 2.57 ± 1.09%, p < 0.01), and kidney (2.69 ± 0.90 vs. 0.53 ± 0.14%, p < 0.01) of C57BL/6N mice 6 days after the administration. Mice pretreated with CD28sa or IPC had less renal injury at 24 h after IRI with attenuation of renal tubular damage and lower serum creatinine compared with the mice that underwent renal IRI alone. The number of infiltrating macrophages in the kidney and IFN-γ secreting CD4⁺ T cells in peripheral blood were diminished in the CD28sa-IR group and the IPC-IR group. The renal protection bestowed by CD28sa or IPC was abolished by anti-CD25 antibody administration. Conclusions: Treg expansion induced by CD28sa ameliorated renal IRI.

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Limb ischemic preconditioning protects against contrast-induced acute kidney injury in rats via phosphorylation of GSK-3β

Cited by 44 publications

References 65 publications

Remote Ischemic Preconditioning for Kidney Protection: GSK3β-Centric Insights Into the Mechanism of Action

Remote Ischemic Preconditioning for Kidney Protection: GSK3β-Centric Insights Into the Mechanism of Action

Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

Superagonistic CD28 Protects against Renal Ischemic Injury by Expansion of Regulatory T-Cell

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