scholarly journals Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis

2021 ◽  
Vol 22 (19) ◽  
pp. 10229
Author(s):  
Guangying Shao ◽  
Jinzhao He ◽  
Jia Meng ◽  
Ang Ma ◽  
Xiaoqiang Geng ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Inflammatory Factors ◽  
Ganoderic Acids ◽  
Renal Ischemia Reperfusion Injury ◽  
Underlying Mechanisms

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of Ganoderma lucidum, have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.

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 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 Deletion of the Gamma Subunit of ENaC in Endothelial Cells Does Not Protect against Renal Ischemia Reperfusion Injury

2021 ◽  
Vol 22 (20) ◽  
pp. 10914
Author(s):  
Stephanie M. Mutchler ◽  
Mahpara Hasan ◽  
Donald E. Kohan ◽  
Thomas R. Kleyman ◽  
Roderick J. Tan
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Α Subunit ◽  
Γ Subunit ◽  
Renal Ischemia Reperfusion Injury

Acute kidney injury due to renal ischemia-reperfusion injury (IRI) may lead to chronic or end stage kidney disease. A greater understanding of the cellular mechanisms underlying IRI are required to develop therapeutic options aimed at limiting or reversing damage from IRI. Prior work has shown that deletion of the α subunit of the epithelial Na+ channel (ENaC) in endothelial cells protects from IRI by increasing the availability of nitric oxide. While canonical ENaCs consist of an α, β, and γ subunit, there is evidence of non-canonical ENaC expression in endothelial cells involving the α subunit. We therefore tested whether the deletion of the γ subunit of ENaC also protects mice from IRI to differentiate between these channel configurations. Mice with endothelial-specific deletion of the γ subunit and control littermates were subjected to unilateral renal artery occlusion followed by 48 h of reperfusion. No significant difference was noted in injury between the two groups as assessed by serum creatinine and blood urea nitrogen, levels of specific kidney injury markers, and histological examination. While deletion of the γ subunit did not alter infiltration of immune cells or cytokine message, it was associated with an increase in levels of total and phosphorylated endothelial nitric oxide synthase (eNOS) in the injured kidneys. Our studies demonstrate that even though deletion of the γ subunit of ENaC may allow for greater activation of eNOS, this is not sufficient to prevent IRI, suggesting the protective effects of α subunit deletion may be due, in part, to other mechanisms.

scholarly journals Temporal and sex-dependent gene expression patterns in a renal ischemia-reperfusion injury and recovery pig model

2021 ◽  
Author(s):  
Stéphane Nemours ◽  
Luis Castro ◽  
Didac Ribatallada-Soriano ◽  
Maria Eugenia Semidey ◽  
Miguel Aranda ◽  
...  
Keyword(s):  
Sex Differences ◽  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Pig Model ◽  
Gene Sets ◽  
Renal Ischemia Reperfusion Injury

ABSTRACTMen are more prone to acute kidney injury (AKI) and chronic kidney disease (CKD), progressing to end-stage renal disease (ESRD) than women. Severity and capacity to regenerate after AKI are important determinants of CKD progression, and of patient morbidity and mortality in the hospital setting. To determine sex differences during injury and recovery we have generated a female and male renal ischemia/reperfusion injury (IRI) pig model, which represents a major cause of AKI. Although no differences were found in blood urea nitrogen (BUN) and serum creatinine (SCr) levels between both sexes, females exhibited higher mononuclear infiltrates at basal and recovery, while males showed more tubular damage at injury. Global transcriptomic analyses of kidney biopsies from our IRI pig model revealed a sexual dimorphism in the temporal regulation of genes and pathways relevant for kidney injury and repair, which was also detected in human samples. Enrichment analysis of gene sets revealed five temporal and four sexual patterns governing renal IRI and recovery. Overall, this study constitutes an extensive characterization of the time and sex differences occurring during renal IRI and recovery at gene expression level and offers a template of translational value for further study of sexual dimorphism in kidney diseases.AUTHOR SUMMARYKidneys’ correct functioning is essential for optimal body homeostasis, being their basic functions blood filtration and excretion of wastes and toxins. Inherited or acquired conditions can cause renal dysfunction requiring renal replacement therapy, which will affect patients’ life quality and survival. A major cause of kidney failure is the renal ischemia/reperfusion injury (IRI), which occurs in many clinical situations like kidney transplantation or aortic aneurysm surgery. Interestingly, men are more susceptible to IRI than women, being women more protected against kidney injury. However, the genetics regulating these sex differences in injury and renal repair remained unknown.Here, we provide a novel porcine model to study renal injury and recovery in both males and females. Using this model, we have identified the gene sets involved in renal injury and recovery processes. Moreover, global genetic analyses allowed us to discover the temporal and sex-dependent patterns that regulate those gene sets and, finally, kidney damage and repair. A relevant finding of our study is that males develop a feminized genetic profile during recovery, which may represent a survival mechanism to diminish the androgenic pro-damage effects on kidney cells. To sum up, our results provide novel sex-dependent targets to prevent renal injury and promote kidney recovery.

scholarly journals Protective Effect of CXCR3+CD4+CD25+Foxp3+Regulatory T Cells in Renal Ischemia-Reperfusion Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Cao Jun ◽  
Li Qingshu ◽  
Wei Ke ◽  
Li Ping ◽  
Dong Jun ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Tubular Necrosis ◽  
Renal Ischemia Reperfusion Injury ◽  
Histology Score

Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

scholarly journals C-reactive protein exacerbates renal ischemia-reperfusion injury

2013 ◽  
Vol 304 (11) ◽  
pp. F1358-F1365 ◽  
Author(s):  
Melissa A. Pegues ◽  
Mark A. McCrory ◽  
Abolfazl Zarjou ◽  
Alexander J. Szalai
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Alternative Activation ◽  
Pcr Analysis ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Renal Ischemia Reperfusion Injury

Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), occurring with hypotension and cardiovascular surgery and inevitably during kidney transplantation. Mortality from AKI is high due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. Inflammation accompanies IRI and increases the blood level of C-reactive protein (CRP), a biomarker of worsened outcomes in AKI. To test if CRP is causal in AKI we subjected wild-type mice (WT) and human CRP transgenic mice (CRPtg) to bilateral renal IRI (both pedicles clamped for 30 min at 37°C then reperfused for 24 h). Serum human CRP level was increased approximately sixfold after IRI in CRPtg (10.62 ± 1.31 μg/ml at baseline vs. 72.01 ± 9.41 μg/ml at 24 h) but was not elevated by sham surgery wherein kidneys were manipulated but not clamped. Compared with WT, serum creatinine, urine albumin, and histological evidence of kidney damage were increased after IRI in CRPtg mice. RT-PCR analysis of mRNA isolated from whole kidneys of CRPtg and WT subjected to IRI revealed that in CRPtg kidneys 1) upregulation of markers of macrophage classical activation (M1 markers) was blunted, 2) downregulation of markers of macrophage alternative activation (M2 markers) was more robust, and 3) expression of the activating receptor FcγRI was increased. Our finding that CRP exacerbates IRI-induced AKI, perhaps by shifting the balance of macrophage activation and FcγR expression towards a detrimental portfolio, might make CRP a promising therapeutic target for the treatment of AKI.

scholarly journals Acute Kidney Injury Induced Lupus Exacerbation Through the Enhanced Neutrophil Extracellular Traps (and Apoptosis) in Fcgr2b Deficient Lupus Mice With Renal Ischemia Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Wilasinee Saisorn ◽  
Supichcha Saithong ◽  
Pornpimol Phuengmaung ◽  
Kanyarat Udompornpitak ◽  
Thansita Bhunyakarnjanarat ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Neutrophil Extracellular Traps ◽  
Renal Ischemia ◽  
Extracellular Traps ◽  
Renal Ischemia Reperfusion Injury ◽  
Syk Inhibitor

Renal ischemia is the most common cause of acute kidney injury (AKI) that might be exacerbate lupus activity through neutrophil extracellular traps (NETs) and apoptosis. Here, the renal ischemia reperfusion injury (I/R) was performed in Fc gamma receptor 2b deficient (Fcgr2b-/-) lupus mice and the in vitro experiments. At 24 h post-renal I/R injury, NETs in peripheral blood neutrophils and in kidneys were detected using myeloperoxidase (MPO), neutrophil elastase (NE) and citrullinated histone H3 (CitH3), as well as kidney apoptosis (activating caspase-3), which were prominent in Fcgr2b-/- mice more compared to wild-type (WT). After 120 h renal-I/R injury, renal NETs (using MPO and NE) were non-detectable, whereas glomerular immunoglobulin (Ig) deposition and serum anti-dsDNA were increased in Fcgr2b-/- mice. These results imply that renal NETs at 24 h post-renal I/R exacerbated the lupus nephritis at 120 h post-renal I/R injury in Fcgr2b-/- lupus mice. Furthermore, a Syk inhibitor attenuated NETs, that activated by phorbol myristate acetate (PMA; a NETs activator) or lipopolysaccharide (LPS; a potent inflammatory stimulator), more prominently in Fcgr2b-/- neutrophils than the WT cells as determined by dsDNA, PAD4 and MPO. In addition, the inhibitors against Syk and PAD4 attenuated lupus characteristics (serum creatinine, proteinuria, and anti-dsDNA) in Fcgr2b-/- mice at 120 h post-renal I/R injury. In conclusion, renal I/R in Fcgr2b-/- mice induced lupus exacerbation at 120 h post-I/R injury partly because Syk-enhanced renal NETs led to apoptosis-induced anti-dsDNA, which was attenuated by a Syk inhibitor.

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