Microbiome-Metabolome Signature of Acute Kidney Injury

Intestinal microbiota play a considerable role in the host’s organism, broadly affecting its organs and tissues. The kidney can also be the target of the microbiome and its metabolites (especially short-chain fatty acids), which can influence renal tissue, both by direct action and through modulation of the immune response. This impact is crucial, especially during kidney injury, because the modulation of inflammation or reparative processes could affect the severity of the resulting damage or recovery of kidney function. In this study, we compared the composition of rat gut microbiota with its outcome, in experimental acute ischemic kidney injury and named the bacterial taxa that play putatively negative or positive roles in the progression of ischemic kidney injury. We investigated the link between serum creatinine, urea, and a number of metabolites (acylcarnitines and amino acids), and the relative abundance of various bacterial taxa in rat feces. Our analysis revealed an increase in levels of 32 acylcarnitines in serum, after renal ischemia/reperfusion and correlation with creatinine and urea, while levels of three amino acids (tyrosine, tryptophan, and proline) had decreased. We detected associations between bacterial abundance and metabolite levels, using a compositionality-aware approach—Rothia and Staphylococcus levels were positively associated with creatinine and urea levels, respectively. Our findings indicate that the gut microbial community contains specific members whose presence might ameliorate or, on the contrary, aggravate ischemic kidney injury. These bacterial taxa could present perspective targets for therapeutical interventions in kidney pathologies, including acute kidney injury.

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MO343SERUM RESPONSE FACTOR, A NOVEL EARLY DIAGNOSTIC BIOMARKER OF ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab084.0016 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Long Zhao ◽

Yan Xu

Keyword(s):

Acute Kidney Injury ◽

Serum Response Factor ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Diagnostic Value ◽

Renal Tissue ◽

Response Factor ◽

Diagnostic Biomarker ◽

Renal Tubular ◽

Early Diagnostic

Abstract Background and Aims Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI). Method AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI. Results Bioinformatics results demonstrated that SRF was dramatically elevated 2-4 h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at 1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively. Conclusion SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.

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Upregulated miR-101 inhibits acute kidney injury–chronic kidney disease transition by regulating epithelial–mesenchymal transition

Human & Experimental Toxicology ◽

10.1177/0960327120937334 ◽

2020 ◽

Vol 39 (12) ◽

pp. 1628-1638 ◽

Cited By ~ 1

Author(s):

J-Y Zhao ◽

X-L Wang ◽

Y-C Yang ◽

B Zhang ◽

Y-B Wu

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renal Tissue ◽

Mesenchymal Transition

Acute kidney injury (AKI) is an independent risk factor for chronic kidney disease (CKD). However, the role and mechanism of microRNA (miRNA, miR) in AKI-CKD transition are elusive. In this study, a murine model of renal ischemia/reperfusion was established to investigate the repairing effect and mechanism of miR-101a-3p on renal injury. The pathological damage of renal tissue was observed by hematoxylin and eosin and Masson staining. The levels of miR-101, profibrotic cytokines, and epithelial–mesenchymal transition (EMT) markers were analyzed using Western blotting, real-time polymerase chain reaction, and/or immunofluorescence. MiR-101 overexpression caused the downregulation of α-smooth muscle actin, collagen-1, and vimentin, as well as upregulation of E-cadherin, thereby alleviating the degree of renal tissue damage. MiR-101 overexpression mitigated hypoxic HK-2 cell damage. Collagen, type X, alpha 1 and transforming growth factor β receptor 1 levels were downregulated in hypoxic cells transfected with miR-101 mimic. Our study indicates that miR-101 is an anti-EMT miRNA, which provides a novel therapeutic strategy for AKI-CKD transition.

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Post-treatment with JP-1302 protects against renal ischemia/reperfusion-induced acute kidney injury in rats

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2018.12.008 ◽

2019 ◽

Vol 139 (3) ◽

pp. 137-142 ◽

Cited By ~ 5

Author(s):

Takaomi Shimokawa ◽

Hidenobu Tsutsui ◽

Takeshi Miura ◽

Masashi Takama ◽

Kohei Hayashi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Post Treatment ◽

Renal Ischemia

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Hydrogen sulfide reduces pyroptosis and alleviates ischemia-reperfusion acute kidney injury by inhibiting NLRP3 inflammasome

Life Sciences ◽

10.1016/j.lfs.2021.119466 ◽

2021 ◽

pp. 119466

Author(s):

Jindi Ni ◽

Lijing Jiang ◽

Guofeng Shen ◽

Zhuye Xia ◽

Lu Zhang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hydrogen Sulfide ◽

Nlrp3 Inflammasome ◽

Ischemia Reperfusion ◽

Kidney Injury

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Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

Cell Death and Disease ◽

10.1038/s41419-021-03578-y ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Yue Zhang ◽

Hongdong Huang ◽

Wenhu Liu ◽

Sha Liu ◽

Xue Yan Wang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Cecal Ligation ◽

Kidney Injury ◽

Renal Tissue ◽

Endothelial Glycocalyx ◽

Endothelial Progenitor ◽

Marker Proteins ◽

Related Transcription Factor

AbstractThe role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

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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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Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-κB pathway in ischemia/reperfusion-induced acute kidney injury

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2014.01.005 ◽

2014 ◽

Vol 444 (2) ◽

pp. 121-127 ◽

Cited By ~ 38

Author(s):

Jae-Won Lee ◽

Sun Chul Kim ◽

Yoon Sook Ko ◽

Hee Young Lee ◽

Eunjung Cho ◽

...

Keyword(s):

Acute Kidney Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renoprotective Effect

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Gene Microarray Integrated with High-Throughput Proteomics for the Discovery of Transthyretin in Rhabdomyolysis-Induced Acute Kidney Injury

Cellular Physiology and Biochemistry ◽

10.1159/000484028 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1673-1688 ◽

Cited By ~ 1

Author(s):

Ou Li ◽

Xiaodong Geng ◽

Qian Ma ◽

Weiwei Wang ◽

Ran Liu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Western Blotting ◽

Kidney Injury ◽

Physical Exertion ◽

Renal Tissue ◽

Gene Microarray ◽

Absolute Quantitation ◽

Gene And Protein Expression ◽

Isobaric Tagging

Background/Aims: Rhabdomyolysis, one of the leading causes of acute kidney injury (AKI), develops after trauma, drug toxicity, infections, burns, and physical exertion. The aim of this study was to investigate differences in gene and protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced AKI. Methods: In this study, we used glycerol induced renal injury as a model of RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene microarray analysis. Isobaric tagging with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between RM-induced AKI and normal murine renal tissue. Verification experiments included immunohistochemistry (IHC), real-time PCR, Western blotting, and the measurement of ATP and ROS production. HK-2 cells were incubated in vitro with ferrous myoglobin and pcDNA-TTR, followed by assays to detect cell proliferation, ROS and apoptosis. Results: According to gene microarray and iTRAQ-MS analysis, we screened 17 common elements. After multiple analyses, we selected transthyretin (TTR) as our focus and investigated TTR in the kidney. Verification experiments with IHC confirmed differential expression levels of TTR proteins. Furthermore, Western blotting showed a stepwise decrease in TTR in AKI renal tissues. Cell-based experiments showed that overexpression of TTR could improve HK-2 cell viability and inhibit apoptosis. TTR reduced apoptosis by decreasing the accumulation of reactive oxygen species (ROS). Conclusion: This study reports a possible mechanism for RM-induced AKI and suggests that reductions in TTR could increase the generation of ROS and induce apoptosis. TTR may be a potentially valuable target for RM-induced AKI.

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