scholarly journals Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chong Huang ◽  
Yan Chen ◽  
Bin Lai ◽  
Yan-Xia Chen ◽  
Cheng-Yun Xu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Akt Pathway ◽  
Acute Renal Injury ◽  
Injury Model ◽  
Renal Ischemia Reperfusion Injury

Abstract Background Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown. Methods An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats. Results The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats. Conclusions SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.

scholarly journals Dexmedetomidine Preconditioning Protects Rats from Renal Ischemia–Reperfusion Injury Accompanied with Biphasic Changes of Nuclear Factor-Kappa B Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Naren Bao ◽  
Bing Tang ◽  
Junke Wang
Keyword(s):  
Reperfusion Injury ◽  
Nuclear Factor Kappa B ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Renal Ischemia Reperfusion Injury ◽  
Anti Inflammatory

Acute kidney injury (AKI) is one of the most common and troublesome perioperative complications. Dexmedetomidine (DEX) is a potent α2-adrenoceptor (α2-AR) agonist with anti-inflammatory and renoprotective effects. In this study, a rat renal ischemia–reperfusion injury (IRI) model was induced. At 24 h after reperfusion, the IRI-induced damage and the renoprotection of DEX preconditioning were confirmed both biochemically and histologically. Changes in nuclear factor-kappa B (NF-κB), as well as its downstream anti-inflammatory factor A20 and proinflammatory factor tumor necrosis factor-α (TNF-α), were detected. Atipamezole, a nonselective antagonist, was then added 5 min before the administration of DEX to further analyze DEX’s effects on NF-κB, and another anti-inflammatory medicine, methylprednisolone, was used in comparison with DEX, to further analyze DEX’s effects on NF-κB. Different concentrations of DEX (0 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM) were applied to preincubated human renal tubular epithelial cell line (HK-2) cells in vitro. After anoxia and reoxygenation, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the levels of NF-κB downstream anti-inflammatory cytokines. The results showed that, unlike methylprednisolone, DEX preconditioning led to a time-dependent biphasic change (first activation then inhibition) of NF-κB in the rat renal IRI models that were given 25 μg/kg i.p. It was accompanied by a similarly biphasic change of TNF-α and an early and persistent upregulation of A20. In vitro, DEX’s cellular protection showed a concentration-dependent biphasic change which was protective within the range of 0 to 100 nM but became opposite when concentrations are greater than 1 μM. The changes in the A20 and NF-κB messenger RNA (mRNA) levels were consistent with the renoprotective ability of DEX. In other words, DEX preconditioning protected the rats from renal IRI via regulation biphasic change of NF-κB signaling.

scholarly journals Tubeimoside-1 Protects Against Renal Ischemia Reperfusion Injury In Vivo and In Vitro

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2097764
Author(s):  
Xiaoli Yuan ◽  
Jing Wang ◽  
Yun Zhang
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury. This study aimed to explore whether tubeimoside-1 (TBMS1) could protect against RIRI. RIRI mice model and hypoxia/reoxygenation (H/R)-induced NRK-52E cells were used in this study. The renal pathology was observed by hematoxylin and eosin staining to calculate the tubular injury score. The levels of serum creatinine and blood urine nitrogen were analyzed by a Hitachi model 7180 automatic analyzer. The expressions of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin 6 (IL-6), Bax, cleaved caspase-3, cleaved caspase-9, total caspase-3, and total caspase-9 in renal tissues and NRK-52E cells were detected by western blot analysis. The levels of TNF-α, IL-1β, and IL-6 in serum and NRK-52E cells were measured by a commercial enzyme-linked immunosorbent assay kit. The renal cell apoptosis in renal tissues was analyzed by TUNEL assay, and NRK-52E cell apoptosis was detected by flow cytometry analysis. CCK-8 assay was used to analyze the viability of NRK-52E cells after the indicated treatment. As a result, the renal tissues that were seriously damaged in mice with RIRI could be alleviated by TBMS1. Therefore, 50 mg/kg TBMS1 was chosen for the animal experiment. Renal cell apoptosis was increased in renal tissues of mice with RIRI. These changes could be partially reversed by TBMS1 treatment. TBMS1 improved the viability, and reduced the inflammation and apoptosis of H/R-induced NRK-52E cells. In conclusion, TBMS1 ameliorates RIRI by promoting viability and suppressing apoptosis and inflammation of renal cells.

scholarly journals Indoleamine 2,3-dioxygenase expression promotes renal ischemia-reperfusion injury

2008 ◽  
Vol 295 (1) ◽  
pp. F226-F234 ◽  
Author(s):  
Kanishka Mohib ◽  
Shuang Wang ◽  
Qiunong Guan ◽  
Andrew L. Mellor ◽  
Hongtao Sun ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Indoleamine 2,3 Dioxygenase ◽  
Renal Ischemia Reperfusion Injury

Indoleamine 2,3-dioxygenase (IDO) catabolizes tryptophan to N-formyl kynurenine and has a proapoptotic role in renal tubular epithelial cells (TEC) in response to IFN-γ and TNF-α in vitro. TEC produce abundant amounts of IDO in vitro in response to inflammation but a pathological role for IDO in renal injury remains unknown. We investigated the role of IDO in a mouse model of renal ischemia-reperfusion injury (IRI). IRI was induced by clamping the renal pedicle of C57BL/6 mice for 45 min at 32°C. Here, we demonstrate upregulation of IDO in renal tissue at 2 h after reperfusion which reached maximal levels at 24 h. Inhibition of IDO following IRI prevented the increase in serum creatinine observed in vehicle-treated mice (86.4 ± 25 μmol/l, n = 11) compared with mice treated with 1-methyl-d-tryptophan, a specific inhibitor of IDO (33.7 ± 8.7 μmol/l, n = 10, P = 0.031). The role of IDO in renal IRI was further supported by results in IDO-KO mice which maintained normal serum creatinine levels (32.5 ± 2.0 μmol/l, n = 6) following IRI compared with wild-type mice (123 ± 30 μmol/l, n = 9, P = 0.008). Our data suggest that attenuation of IDO expression within the kidney may represent a novel strategy to reduce renal injury as a result of ischemia reperfusion.

scholarly journals The role of arachidonic acid in a rat renal ischemia-reperfusion injury model

2008 ◽  
Author(s):  
Masahide Matsuyama ◽  
Rikio Yoshimura ◽  
Kiyoaki Funao ◽  
Yutaka Kawahito ◽  
Hajime Sano ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Injury Model ◽  
Renal Ischemia Reperfusion Injury

Oxidized LDL Accumulation in Experimental Renal Ischemia Reperfusion Injury Model

Renal Failure ◽  
2007 ◽  
Vol 29 (4) ◽  
pp. 409-415 ◽  
Author(s):  
Eyup Kulah ◽  
Oge Tascilar ◽  
Serefden Acikgoz ◽  
Guldeniz Karadeniz ◽  
Ishak Ozel Tekin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Oxidized Ldl ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Injury Model ◽  
Renal Ischemia Reperfusion Injury

scholarly journals Inhibition of Endothelial PHD2 Suppresses Post-Ischemic Kidney Inflammation through Hypoxia-Inducible Factor-1

2020 ◽  
Vol 31 (3) ◽  
pp. 501-516 ◽  
Author(s):  
Ganeshkumar Rajendran ◽  
Michael P. Schonfeld ◽  
Ratnakar Tiwari ◽  
Shengping Huang ◽  
Rafael Torosyan ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Oxygen Sensor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Inflammatory Cells ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

BackgroundProlyl-4-hydroxylase domain-containing proteins 1–3 (PHD1 to PHD3) regulate the activity of the hypoxia-inducible factors (HIFs) HIF-1 and HIF-2, transcription factors that are key regulators of hypoxic vascular responses. We previously reported that deficiency of endothelial HIF-2 exacerbated renal ischemia-reperfusion injury, whereas inactivation of endothelial PHD2, the main oxygen sensor, provided renoprotection. Nevertheless, the molecular mechanisms by which endothelial PHD2 dictates AKI outcomes remain undefined.MethodsTo investigate the function of the endothelial PHD2/HIF axis in ischemic AKI, we examined the effects of endothelial-specific ablation of PHD2 in a mouse model of renal ischemia-reperfusion injury. We also interrogated the contribution of each HIF isoform by concurrent endothelial deletion of both PHD2 and HIF-1 or both PHD2 and HIF-2.ResultsEndothelial deletion of Phd2 preserved kidney function and limited transition to CKD. Mechanistically, we found that endothelial Phd2 ablation protected against renal ischemia-reperfusion injury by suppressing the expression of proinflammatory genes and recruitment of inflammatory cells in a manner that was dependent on HIF-1 but not HIF-2. Persistence of renoprotective responses after acute inducible endothelial-specific loss of Phd2 in adult mice ruled out a requirement for PHD2 signaling in hematopoietic cells. Although Phd2 inhibition was not sufficient to induce detectable HIF activity in the kidney endothelium, in vitro experiments implicated a humoral factor in the anti-inflammatory effects generated by endothelial PHD2/HIF-1 signaling.ConclusionsOur findings suggest that activation of endothelial HIF-1 signaling through PHD2 inhibition may offer a novel therapeutic approach against ischemic AKI.

scholarly journals Blocking neutrophil integrin activation prevents ischemia–reperfusion injury

2015 ◽  
Vol 212 (8) ◽  
pp. 1267-1281 ◽  
Author(s):  
Tadayuki Yago ◽  
Brian G. Petrich ◽  
Nan Zhang ◽  
Zhenghui Liu ◽  
Bojing Shao ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Integrin Activation ◽  
Β2 Integrin ◽  
Renal Ischemia Reperfusion Injury ◽  
Slow Rolling

Neutrophil recruitment, mediated by β2 integrins, combats pyogenic infections but also plays a key role in ischemia–reperfusion injury and other inflammatory disorders. Talin induces allosteric rearrangements in integrins that increase affinity for ligands (activation). Talin also links integrins to actin and other proteins that enable formation of adhesions. Structural studies have identified a talin1 mutant (L325R) that perturbs activation without impairing talin’s capacity to link integrins to actin and other proteins. Here, we found that mice engineered to express only talin1(L325R) in myeloid cells were protected from renal ischemia–reperfusion injury. Dissection of neutrophil function in vitro and in vivo revealed that talin1(L325R) neutrophils had markedly impaired chemokine-induced, β2 integrin–mediated arrest, spreading, and migration. Surprisingly, talin1(L325R) neutrophils exhibited normal selectin-induced, β2 integrin–mediated slow rolling, in sharp contrast to the defective slow rolling of neutrophils lacking talin1 or expressing a talin1 mutant (W359A) that blocks talin interaction with integrins. These studies reveal the importance of talin-mediated activation of integrins for renal ischemia–reperfusion injury. They further show that neutrophil arrest requires talin recruitment to and activation of integrins. However, although neutrophil slow rolling requires talin recruitment to integrins, talin-mediated integrin activation is dispensable.

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