The Ameliorating Effect of Plasma Protein from Tachypleus tridentatus on Cyclophosphamide-Induced Acute Kidney Injury in Mice

In the study, the protective effect of plasma protein from Tachypleus tridentatus (PPTT) on acute kidney injury (AKI) and the related molecular mechanisms were first investigated by Western blotting analyses, TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, and immunohistochemistry. It was found that PPTT had an obviously inhibitory effect on Reactive oxygen species (ROS) in cyclophosphamide (CTX)-exposed mice. Furthermore, results demonstrated that the renal cell death mode is due to inducing apoptosis and autophagy inhibited by dose-dependent PPTT in mice treated with CTX by decreasing the protein expression of bax, beclin-1, and LC3 and increasing the expression of bcl-2. Moreover, the p38 MAPK and PI3K/Akt signaling pathways were observed to take part in the PPTT-induced renal cell growth effect by enhancing the upregulation of the expression of Akt and p-Akt as well as the downregulation of the expression of p38 and p-p38, which indicated a PPTT ameliorating effect on AKI CTX-induced in mice through p38 MAPK and PI3K/Akt signaling pathways. Briefly, this article preliminarily studies the mechanism of the PPTT ameliorating effect on AKI CTX-induced in mice, which helps to provide a reference for PPTT clinical application in AKI therapy.

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Remote Ischemic Preconditioning Protects Cisplatin-Induced Acute Kidney Injury through the PTEN/AKT Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7629396 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Wanfen Zhang ◽

Cheng Chen ◽

Ran Jing ◽

Tongqiang Liu ◽

Bicheng Liu

Keyword(s):

Acute Kidney Injury ◽

Ischemic Preconditioning ◽

Therapeutic Strategy ◽

Molecular Mechanisms ◽

Kidney Injury ◽

Akt Signaling ◽

Remote Ischemic Preconditioning ◽

Pten Mrna ◽

Induce Resistance ◽

In Cis

Although cisplatin (Cis) is an effective chemotherapeutic agent in treatment of various cancers, its adverse effect of nephrotoxicity limits the clinical application. Remote ischemic preconditioning (RIPC) is a strategy to induce resistance in a target organ against the oxidative stress and injury by applying transient, brief episodes of ischemia. However, whether RIPC exerts protective effect on Cis-induced renal injury remains unclear. In this study, we showed that RIPC significantly alleviated the renal functional and histopathological damage of Cis-induced acute kidney injury (AKI) mice. Furthermore, RIPC substantially reversed the downregulation of miR-144 and upregulation of PTEN in renal tissues of Cis-induced AKI mice and alleviated tubular cell apoptosis via activating PTEN/AKT signaling. In mechanism, we demonstrated that miR-144 directly targets the 3’-UTR of PTEN mRNA, and then the elevation of miR-144 in RIPC activates PTEN/AKT signaling by downregulating PTEN expression to achieve its antiapoptosis effect. Collectively, our results indicate that RIPC may be a potential therapeutic strategy in Cis-induced AKI, and provide insights on the underlying molecular mechanisms of cisplatin’s nephrotoxicity.

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The Suppression of Pin1-Alleviated Oxidative Stress through the p38 MAPK Pathway in Ischemia- and Reperfusion-Induced Acute Kidney Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/1313847 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Xiaojie Zhao ◽

Dan Wang ◽

Shanshan Wan ◽

Xiuheng Liu ◽

Wei Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

P38 Mapk ◽

Molecular Mechanisms ◽

Mapk Pathway ◽

Kidney Injury ◽

Ischemia And Reperfusion ◽

P38 Mapk Pathway

Background. Pin1, as the peptidyl-prolyl isomerase, plays a vital role in cellular processes. However, whether it has a regulatory effect on renal ischemia and reperfusion (I/R) injury still remains unknown. Methods. The hypoxia/reoxygenation (H/R) model in human kidney (HK-2) cells and the I/R model in rats were assessed to investigate the role of Pin1 on I/R-induced acute kidney injury. Male Sprague-Dawley rats were used to establish the I/R model for 15, 30, and 45 min ischemia and then 24 h reperfusion, with or without the Pin1 inhibitor, to demonstrate the role of Pin1 in acute kidney injury. HK-2 cells were cultured and experienced the H/R model to identify the molecular mechanisms involved. Results. In this study, we found that Pin1 and oxidative stress were obviously increased after renal I/R. Inhibition of Pin1 with juglone decreased renal structural and functional injuries, as well as oxidative stress. Besides, Pin1 inhibition with the inhibitor, juglone, or the small interfering RNA showed significant reduction on oxidative stress markers caused by the H/R process in vitro. Furthermore, the results indicated that the expression of p38 MAPK was increased during H/R in vitro and Pin1 inhibition could reduce the increased expression of p38 MAPK. Conclusion. Our results illustrated that Pin1 aggravated renal I/R injury via elevating oxidative stress through activation of the p38 MAPK pathway. These findings indicated that Pin1 might become the potential treatment for renal I/R injury.

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A Porthole over AKI: Cell Dynamics in Damage and Repair

Nephron ◽

10.1159/000508504 ◽

2020 ◽

Vol 144 (12) ◽

pp. 650-654

Author(s):

Luca Bordoni ◽

Donato Sardella ◽

Ina Maria Schiessl

Keyword(s):

Acute Kidney Injury ◽

Renal Cell ◽

Kidney Injury ◽

Cell Types ◽

Cell Interactions ◽

Intravital Imaging ◽

Cell Dynamics ◽

Powerful Technique ◽

Increased Risk ◽

Cell Crosstalk

Acute kidney injury (AKI) is associated with an increased risk of CKD. Injury-induced multifaceted renal cell-to-cell crosstalk can either lead to successful self-repair or chronic fibrosis and inflammation. In this mini-review, we will discuss critical renal cell types acting as victims or executioners in AKI pathology and introduce intravital imaging as a powerful technique to further dissect these cell-to-cell interactions.

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MBD2 mediates renal cell apoptosis via activation of Tox4 during rhabdomyolysis‐induced acute kidney injury

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.16207 ◽

2021 ◽

Author(s):

Tianshi Sun ◽

Qing Liu ◽

Yifan Wang ◽

Youwen Deng ◽

Dongshan Zhang

Keyword(s):

Acute Kidney Injury ◽

Cell Apoptosis ◽

Renal Cell ◽

Kidney Injury

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miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury

Renal Failure ◽

10.1080/0886022x.2021.1871922 ◽

2021 ◽

Vol 43 (1) ◽

pp. 291-301

Author(s):

Caifa Zheng ◽

Dansen Wu ◽

Songjing Shi ◽

Liming Wang

Keyword(s):

Acute Kidney Injury ◽

Renal Cell ◽

Kidney Injury ◽

Aquaporin 2

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TGF-β1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells

FEBS Journal ◽

10.1111/febs.14201 ◽

2017 ◽

Vol 284 (20) ◽

pp. 3437-3454 ◽

Cited By ~ 41

Author(s):

Ana Rodríguez-García ◽

Paula Samsó ◽

Pere Fontova ◽

Helga Simon-Molas ◽

Anna Manzano ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

P38 Mapk ◽

Akt Signaling ◽

Glioblastoma Cells ◽

Tgf Β1

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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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Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Hereditas ◽

10.1186/s41065-021-00176-y ◽

2021 ◽

Vol 158 (1) ◽

Author(s):

Yun Tang ◽

Xiaobo Yang ◽

Huaqing Shu ◽

Yuan Yu ◽

Shangwen Pan ◽

...

Keyword(s):

Gene Expression ◽

Septic Shock ◽

Acute Kidney Injury ◽

Molecular Mechanisms ◽

Therapeutic Targets ◽

Kidney Injury ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Blood Samples ◽

Potential Biomarkers

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

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miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury

Kidney Diseases ◽

10.1159/000520140 ◽

2021 ◽

pp. 1-11

Author(s):

Yue Zhao ◽

Yue Lang ◽

Mingchao Zhang ◽

Shaoshan Liang ◽

Xiaodong Zhu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Molecular Mechanisms ◽

Mitochondrial Dynamics ◽

Kidney Injury ◽

Immunofluorescent Staining ◽

Luciferase Reporter ◽

Mitochondrial Fragmentation ◽

Tubular Cells ◽

Renal Tubular Cells

Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. Objectives: To explore the molecular mechanisms of mitochondrial disorders and kidney damage. Methods: We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. Results: miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.

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