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

AbstractOur previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

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Heme oxygenase-1 induction mitigates burn-associated early acute kidney injury via the TLR4 signaling pathway

Burns ◽

10.1016/j.burns.2021.04.013 ◽

2021 ◽

Author(s):

Songxue Guo ◽

Meirong Yu ◽

Quan Fang ◽

Liping Zhang ◽

Chuangang You ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Tlr4 Signaling ◽

Tlr4 Signaling Pathway

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DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury

Cell Death Discovery ◽

10.1038/s41420-021-00528-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yinwu Bao ◽

Mengqiu Bai ◽

Huanhuan Zhu ◽

Yuan Yuan ◽

Ying Wang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Cell Injury ◽

Inflammatory Responses ◽

Kidney Injury ◽

Renal Tissue ◽

Clinical Samples ◽

Mice Model ◽

Expression Levels ◽

Ppar Signaling

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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Protective Effect of Taurine on Mice with Doxorubicin-induced Acute Kidney Injury

Advances in Experimental Medicine and Biology - Taurine 10 ◽

10.1007/978-94-024-1079-2_95 ◽

2017 ◽

pp. 1191-1201 ◽

Cited By ~ 7

Author(s):

Yon-Suk Kim ◽

Si-Heung Sung ◽

Yujiao Tang ◽

Eun-Ju Choi ◽

Young-Jin Choi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Protective Effect ◽

Kidney Injury

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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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Canagliflozin protects against cisplatin-induced acute kidney injury by AMPK-mediated autophagy in renal proximal tubular cells

Cell Death Discovery ◽

10.1038/s41420-021-00801-9 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Cheol Ho Park ◽

Bin Lee ◽

Myeonggil Han ◽

Woo Joong Rhee ◽

Man Sup Kwak ◽

...

Keyword(s):

Acute Kidney Injury ◽

Protective Effect ◽

Kidney Injury ◽

Proximal Tubular Cells ◽

Cell Viability Assay ◽

Tubular Cells ◽

Compound C ◽

Proximal Tubular ◽

Renal Proximal Tubular Cells ◽

Renal Proximal Tubular

AbstractSodium-glucose cotransporter 2 inhibitors, which are recently introduced as glucose-lowering agents, improve cardiovascular and renal outcomes in patients with diabetes mellitus. These drugs also have beneficial effects in various kidney disease models. However, the effect of SGLT2 inhibitors on cisplatin-induced acute kidney injury (AKI) and their mechanism of action need to be elucidated. In this study, we investigated whether canagliflozin protects against cisplatin-induced AKI, depending on adenosine monophosphate-activated protein kinase (AMPK) activation and following induction of autophagy. In the experiments using the HK-2 cell line, cell viability assay and molecular analysis revealed that canagliflozin protected renal proximal tubular cells from cisplatin, whereas addition of chloroquine or compound C abolished the protective effect of canagliflozin. In the mouse model of cisplatin-induced AKI, canagliflozin protected mice from cisplatin-induced AKI. However, treatment with chloroquine or compound C in addition to administration of cisplatin and canagliflozin eliminated the protective effect of canagliflozin. Collectively, these findings indicate that canagliflozin protects against cisplatin-induced AKI by activating AMPK and autophagy in renal proximal tubular cells.

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Platycodin D Ameliorates Acute Kidney Injury in Septic Rats by Regulating Mitogen Activated Protein Kinase Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:270-276 ◽

2020 ◽

Vol 19 (3) ◽

pp. 270-276

Author(s):

Jianying Wang ◽

Xiaoting Yu

Keyword(s):

Acute Kidney Injury ◽

Protein Kinase ◽

Protective Effect ◽

Cecal Ligation ◽

Kidney Injury ◽

B Cell Lymphoma ◽

Mitogen Activated Protein Kinase ◽

Cecal Ligation And Puncture ◽

Platycodin D ◽

Mitogen Activated Protein

Acute kidney injury is a severe complication of sepsis. We have shown a protective effect of Platycodin D on sepsis induced acute kidney injury in an animal model that employs cecal ligation and puncture. Cecal ligation and puncture induced a series of degenerative changes in kidney, such as edema, hyperemia, and expansion in glomerular capillary, and inflammatory cells infiltration that were attenuated by Platycodin D. Also, rise in proinflammatory cytokine levels in septic rats was blunted by Platycodin D. Furthermore, Platycodin D administration reduced rise in serum levels of kidney injury markers-blood urea nitrogen and serum creatinine-in septic rats. Moreover, Platycodin D administration also suppressed the cell apoptosis in kidney that was associated with enhanced B-cell lymphoma 2 protein and reduced cleaved cysteine-aspartic protease-3 and BCL2-associated X protein. Lastly, Platycodin D administration attenuated sepsis-induced increase of phospho (p)-extracellular signal-regulated kinase, p-c-Jun NH2-terminal kinase, and p-p38. In conclusion, Platycodin D demonstrated protective effect against sepsis induced acute kidney injury through inactivation of mitogen activated protein kinase pathways, thus providing promising therapeutic strategy for the treatment of sepsis.

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