Limb ischemic preconditioning ameliorates renal microcirculation through activation of PI3K/Akt/eNOS signaling pathway after acute kidney injury

AbstractDemethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

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SP157INVESTIGATION OF THE PROTECTIVE EFFECTS OF ATORVASTATION ON CONTRAST-INDUCED ACUTE KIDNEY INJURY FROM THE PERSPECTIVE OF THE TLRA/MYD88 SIGNALING PATHWAY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx142 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii166-iii166

Author(s):

Rongzheng Yue ◽

Chuan Zuo ◽

Jing Zeng ◽

Baihai Su ◽

Ye Tao ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Kidney Injury ◽

Protective Effects ◽

Myd88 Signaling

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Remote Ischemic Preconditioning to Prevent Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.601470 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zigang Liu ◽

Yongmei Zhao ◽

Ming Lei ◽

Guancong Zhao ◽

Dongcheng Li ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Randomized Controlled Trials ◽

Ischemic Preconditioning ◽

Meta Analysis ◽

Kidney Injury ◽

Controlled Trials ◽

Randomized Controlled ◽

Subgroup Analyses ◽

Meta Regression

Objective: Randomized controlled trials (RCTs) evaluating the influence of remote ischemic preconditioning (RIPC) on acute kidney injury (AKI) after cardiac surgery showed inconsistent results. We performed a meta-analysis to evaluate the efficacy of RIPC on AKI after cardiac surgery.Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Meta-regression and subgroup analyses were used to determine the source of heterogeneity.Results: Twenty-two RCTs with 5,389 patients who received cardiac surgery −2,702 patients in the RIPC group and 2,687 patients in the control group—were included. Moderate heterogeneity was detected (p for Cochrane's Q test = 0.03, I2 = 40%). Pooled results showed that RIPC significantly reduced the incidence of AKI compared with control [odds ratio (OR): 0.76, 95% confidence intervals (CI): 0.61–0.94, p = 0.01]. Results limited to on-pump surgery (OR: 0.78, 95% CI: 0.64–0.95, p = 0.01) or studies with acute RIPC (OR: 0.78, 95% CI: 0.63–0.97, p = 0.03) showed consistent results. Meta-regression and subgroup analyses indicated that study characteristics, including study design, country, age, gender, diabetic status, surgery type, use of propofol or volatile anesthetics, cross-clamp time, RIPC protocol, definition of AKI, and sample size did not significantly affect the outcome of AKI. Results of stratified analysis showed that RIPC significantly reduced the risk of mild-to-moderate AKI that did not require renal replacement therapy (RRT, OR: 0.76, 95% CI: 0.60–0.96, p = 0.02) but did not significantly reduce the risk of severe AKI that required RRT in patients after cardiac surgery (OR: 0.73, 95% CI: 0.50–1.07, p = 0.11).Conclusions: Current evidence supports RIPC as an effective strategy to prevent AKI after cardiac surgery, which seems to be mainly driven by the reduced mild-to-moderate AKI events that did not require RRT. Efforts are needed to determine the influences of patient characteristics, procedure, perioperative drugs, and RIPC protocol on the outcome.

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Identification of hub genes and networks in cisplatin-induced acute kidney injury

10.21203/rs.3.rs-1069475/v1 ◽

2021 ◽

Author(s):

Lingyun Yang ◽

Jinwen Xu ◽

Xunwei Liu ◽

Yun Cheng ◽

Hongxia Zhou ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathways ◽

Signaling Pathway ◽

Health Hazard ◽

Herbal Medicines ◽

Kidney Injury ◽

Hub Genes ◽

Chinese Herbal Medicines ◽

Chinese Herbal ◽

Ppi Networks

Abstract Acute kidney injury induced by cisplatin poses a serious health hazard to patients. Thus, this study was undertaken to elucidate key signaling pathways and hub genes relevant for therapeutic intervention involved in cisplatin-induced acute kidney injury(CI-AKI) by bioinformatics. We identified differentially expressed genes(DEGs) by R language on GSE106993 and GSE153625 datasets, downloaded from Gene Expression Omnibus (GEO). GO enrichment analysis and KEGG analysis were used to identify the main functions of common differential genes. The STRING database was used to construct protein-protein interaction (PPI) networks and hub genes were selected by Cytoscape. TransmiR v2.0 database and miRWalk2.0 database were used to construct transcription factor (TF)/microRNA (miRNA)/mRNA networks. Chinese herbal medicines targeting hub genes were screened by the ETMC database. 817 up-regulated genes and 769 down-regulated genes were obtained in CI-AKI model. Tumor necrosis factor(TNF) signaling pathway, P53 signaling, and metabolic signaling pathway are important pathways in CI-AKI. 8 hub genes were identified through PPI (Trp53、Egf、Stat3、Jun、Casp3、Cdh1、Ptgs2、Cat). We also constructed TF/microRNA/mRNA regulatory networks, including 2 TFs, 4 miRNAs and 214 mRNAs. The results of ETMC database analysis showed that Sang-Ye and Ban-Xia could be used for the treatment of CI-AKI. In this study, we identified 8 hub genes and 3 important signaling pathways in CI-AKI model by bioinformatics analysis, which provide targets for the treatment of CI-AKI. And the two Chinese herbal medicines obtained from our research, Sang-Ye and Ban-Xia, are expected to be used for the treatment of CI-AKI. Meanwhile, the TF/miRNA/mRNA networks we constructed are helpful to the further study of the mechanism of CI-AKI.

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Protective effect of hydroxysafflor yellow A against acute kidney injury via the TLR4/NF-κB signaling pathway

Scientific Reports ◽

10.1038/s41598-018-27217-3 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 14

Author(s):

Juan Bai ◽

Jinyi Zhao ◽

Dongxiao Cui ◽

Fan Wang ◽

Ying Song ◽

...

Keyword(s):

Acute Kidney Injury ◽

Protective Effect ◽

Signaling Pathway ◽

Kidney Injury ◽

Hydroxysafflor Yellow A

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Regulator 1-Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Signaling Pathway in Investigating the Pathological Characteristics and Molecular Mechanism of Liver Cirrhosis Complicated by Acute Kidney Injury

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2859 ◽

2022 ◽

Vol 12 (1) ◽

pp. 112-120

Author(s):

Jieqi Gong ◽

Huanhua Lu

Keyword(s):

Acute Kidney Injury ◽

Liver Cirrhosis ◽

Signaling Pathway ◽

Molecular Mechanism ◽

Kidney Injury ◽

Male Rats ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Duct Ligation

The objective of this study was to investigate the molecular mechanism of the histopathological characteristics of liver cirrhosis (LC) complicated with acute kidney injury (AKI) and the signaling pathway of silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) during the pathogenesis of LC. 20 healthy male rats with AKI complicated by laparoscopic cholecystectomy were selected and divided randomly into control group (C group), lipopolysaccharide (LPS) group, bile duct ligation (BDL) group, and model group (lipopolysaccharide+BDL) (D group). The indexes of all the rats were determined, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), sarcoplasmic enzyme (Scr), and blood urea nitrogen (BUN); the SIRT1 and PGC-1α expressions in renal tissues of rats from each group was detected. Results showed that the AST and ALT levels in BDL group and D group were higher markedly than those before surgery (P < 0.05). The serum levels of Scr and BUN in D group 4 hours after LPS injection increased hugely compared with before injection (P < 0.05). Compared with BDL group, the protein levels of SIRT1 and PGC-1α in renal tissue of group D were decreased sharply (P < 0.05), and the SIRT1 protein expression was positively correlated with PGC-1α (r = 0.836 and P < 0.01). When LC were complicated with AKI, SIRT1 activity was reduced and PGC-1α expression was inhibited. Moreover, SIRT1-PGC-1α signaling pathway played a protective role in pathogenesis of LC complicated with AKI.

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Protopine Protects Mice against LPS-Induced Acute Kidney Injury by Inhibiting Apoptosis and Inflammation via the TLR4 Signaling Pathway

Molecules ◽

10.3390/molecules25010015 ◽

2019 ◽

Vol 25 (1) ◽

pp. 15 ◽

Cited By ~ 3

Author(s):

Beibei Zhang ◽

Mengnan Zeng ◽

Meng Li ◽

Yuxuan Kan ◽

Benke Li ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Signaling Pathway ◽

Interleukin 2 ◽

Small Animal ◽

Kidney Injury ◽

Interleukin 10 ◽

Tlr4 Signaling ◽

Tlr4 Signaling Pathway ◽

Apoptosis And Inflammation

Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-γ (IFN-γ), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.

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