Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats

Shen, Xiaohua; Hu, Bo; Xu, Guangtao; Chen, Fengjuan; Ma, Ruifen; Zhang, Nenghua; Liu, Jie; Ma, Xiaoqin; Zhu, Jia; Wu, Yuhong; Shen, Ruilin

doi:10.1159/000477947

Cited by 49 publications

(38 citation statements)

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“…It was found in our study that the activity of SOD and GSH level were decreased while the MDA level was increased in the renal tissue in diabetic RI/RI, demonstrating an oxidative injury. During the process of I/R injury, inflammatory reactions are activated, resulting in the formation of inflammatory cytokines, such as IL-6 and IL-10 [9, 27, 43, 44]. We also found that the expressions of IL-10 and IL-6 in the renal tissue were elevated in this diabetic RI/RI model.…”

Section: Discussionmentioning

confidence: 54%

“…The damage quantification from ten areas corresponding to the renal tissue was graded using the following parameters: tubular cell necrosis, apoptosis, cytoplasmic vacuole formation, hemorrhage, and tubular dilatation based on a five-score system (1, histopathological changes <10%; 2, = 10-25%; 3, =25-50%; 4, =50-75%; and 5, =75-100%). The mean score for each parameter was calculated and subjected to statistical analysis [9, 30]. …”

Section: Methodsmentioning

confidence: 99%

“…In such a condition, patients may need renal transplantation in their later life when diabetic nephropathy occurs [7]. It is assumed that in diabetic rats, a comparatively short ischemia of 30 minutes is a predisposing factor contributing to the reversible acute kidney injury (AKI), causing a progressive injury with early-stage renal failure [4, 8, 9]. Clarification of the underlying mechanism is pivotal for determining efficacious management for diabetic RI/RI.…”

Section: Introductionmentioning

confidence: 99%

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Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Hu¹,

Tong²,

Xu³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). Methods: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

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Section: Discussionmentioning

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Hu¹,

Tong²,

Xu³

et al. 2018

Kidney Blood Press Res

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“…No. 638320, TAKARA) [11]. Reactions were run in a 96-well plate using StepOnePlus system (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Physiological Signatures of Dual Embryonic Origins in Mouse Skull Vault

Zhao

et al. 2017

Cell Physiol Biochem

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Background/Aims: The mammalian skull vault is a highly regulated structure and consists of several membrane bones of different tissue origins (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Although membrane bones form through intramembranous ossification, neural crest derived frontal bone has superior osteoblast activity and bone regeneration ability, triggering a novel conception for craniofacial reconstruction and bone regeneration called endogenous calvarial regeneration. However, a comprehensive landscape of the genes and signaling pathways involved in this process is not clear. Methods: Transcriptome analysis within the two bone elements is firstly performed to determine the physiological signatures of differential gene expressions in mouse skull vault. Results: Frontal bone tissues and parietal bone tissues maintain tissue origin through special gene expression similar to neural crest vs mesoderm tissue, and physiological functions between these two tissues are also found in differences related to proliferation, differentiation and extracellular matrix production and clustered signaling pathways. Conclusion: Our data provide novel insights into the potential gene regulatory network in regulating the development of neural crest-derived frontal bone and mesoderm-derived parietal bone.

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“…The detailed method was essentially as described in the previous literature [43, 44]. Briefly, the myocardial tissues were homogenized in protein lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy

Tong¹,

Zhang²

2018

Cell Physiol Biochem

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Background/Aims: The purpose of this study was to investigate the effect of administering particulate matter (PM_2.5) to the lungs on the sensitivity to myocardial ischemia/reperfusion injury (MI/RI) and the role of farnesoid-X-receptor (FXR)-induced autophagy in this process. Methods: Male Sprague Dawley (SD) rats were subjected to 45 min of ischemia, and the lungs were exposed to 2.0 mg of PM_2.5 in 0.3 mL of normal saline 5 min before reperfusion. After 24 h of reperfusion, the blood and myocardium were collected, and the myocardial infarct sizes, activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH), and levels of serum high sensitivity C-reactive protein (hsCRP), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cardiac troponin T (cTnT), P-selectin and D-dimer were measured via biochemical analysis. Additionally, the myeloperoxidase (MDA) content and superoxide dismutase (SOD) activity were measured in myocardial tissues via biochemical analysis, and the levels of reactive oxygen species (ROS), autophagosomes, microtubule-associated protein 1 light chain 3 (LC-I and II), macrophage inflammatory protein-2 (MIP-2) and farnesoid-X-receptor (FXR) were determined in myocardial tissues via biochemical analysis, immunohistochemical and biochemical techniques and western blot. In addition, the myocardial infarct sizes, LC-I and II expressions were determined in myocardial tissues through FXR^-/- and WT mice. Results: Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in I/R group than that in Sham group, and Levels of IL-4 and SOD were lower in I/R group than that in Sham group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in I/R group than that in Sham group. Levels of CK, LDH, hsCRP, IL-6, TNF-α, cTnT, P-selectin and D-dimer, MDA and infarct sizes were higher in PM_2.5 group than that in I/R group, and Levels of IL-4 and SOD were lower in PM_2.5 group than that in I/R group; ROS, autophagosomes, LC-3I, LC-3II, MIP-2 and FXR expressions were higher in PM_2.5 group than that in I/R group. Conclusions: PM_2.5 post-treatment exacerbated myocardial injury partly through upregulation of FXR to induce autophagy compared to MI/RI.

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Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats

Cited by 49 publications

References 50 publications

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Physiological Signatures of Dual Embryonic Origins in Mouse Skull Vault

Pulmonary Exposure to Particulate Matter (PM2.5) Affects the Sensitivity to Myocardial Ischemia/Reperfusion Injury Through Farnesoid-X-Receptor-Induced Autophagy

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