Identifying cell-enriched miRNAs in kidney injury and repair

Connor, Katie; Teenan, Oliver; Cairns, Carolynn; Banwell, Victoria; Thomas, Ruth; Rodor, Julie; Finnie, Sarah; Pius, Riinu; Tannahill, Gillian M.; Sahni, Vishal; Savage, Caroline O.S.; Hughes, Jeremy; Henderson, Robert B.; Marson, Lorna; Conway, Bryan; Wigmore, Stephen J.; Denby, Laura

doi:10.1172/jci.insight.140399

Cited by 24 publications

(17 citation statements)

References 61 publications

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“…Since most of the findings were obtained using exogenously expressed miRNAs, further studies are required to evaluate the translational potential of our results. Nonetheless, our findings are consistent with the observation of miR-24 expression in endothelial cells [42][43][44]87] and its roles as a regulator of various cerebrovascular phenomena, including angiogenesis in gliomas [88,89] and vasospasm following subarachnoid hemorrhage [90]. The study also has some strengths, including the fact that the 3 -UTR of Neuropilin-1 that is targeted by miR-24 is highly conserved among species, from primates to rodents.…”

Section: Discussionsupporting

confidence: 90%

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

Mone

Gambardella

Wang

et al. 2021

ncRNA

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Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model.

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Section: Discussionsupporting

confidence: 90%

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

Mone

Gambardella

Wang

et al. 2021

ncRNA

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“…Yin et al [19] have pointed out that lncRNA NETA1 promotes the upregulation of BRD4 via sponge adsorption of miR-16-5p and further aggravates the development of sepsis-induced lung injury. In the process of induction of sepsis to AKI, some people hold a view that miR-16-5p participates in autophagy of kidney tissue by targeting mTORC protein [14,20], and there is also evidence that miR-16-5p suppresses the release of proinflammatory macrophages as a urine biomarker of AKI and then regulates the renal inflammatory response [21]. Based on the above research and the results of the present study, the downregulation of miR-16-5p is probably a landmark event of SI-AKI, during which the downregulation promotes the pathophysiological process of SI-AKI through macrophage polarization conversion and autophagy mediated by the mTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

Evaluation Value of Serum miR-4299 and miR-16-5p in Risk Stratification of Sepsis-Induced Acute Kidney Injury

Pan¹,

Zhang²,

Hu³

et al. 2022

BioMed Research International

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Objective. This study was designed to determine the evaluation value of serum miR-4299 and miR-16-5p in risk stratification of sepsis-induced acute kidney injury (SI-AKI). Methods. A total of 115 sepsis patients were enrolled and assigned to the SI-AKI group ( n = 64 ) or the sepsis-non-AKI group ( n = 51 ) based on the occurrence of AKI, and 72 healthy individuals were enrolled. Fasting venous blood was sampled from every patient before admission, before therapy, and after therapy, followed by quantification of miR-4299 and miR-16-5p by fluorescence quantitative PCR. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of serum miR-16-5p and miR-4299 expression in predicting SI-AKI, and Pearson’s correlation analysis was performed to explore the associations of the two with Scr, Cys-C, and KIM-1. Results. Cases with sepsis, especially SI-AKI, presented significantly downregulated serum miR-4299 and miR-16-5p. After therapy, the expression in them increased. The area under curve (AUC) of serum miR-4299 and miR-16-5p in the prediction value for early diagnosis of SI-AKI was 0.895 (95% CI: 0.839-0.951, cutoff value: 0.780) and 0.838 (95% CI: 0.767-0.909, cutoff value: 0.775), respectively, and the AUC of them in the prediction value for clinical efficacy on the disease were 0.733 (95% CI: 0.645-0.820, cutoff value: 1.115) and 0.776 (95% CI: 0.698-0.855, cutoff value: 1.125), respectively. Serum miR-16-5p and mIR-4299 were negatively correlated with Scr, Cys-C, and KIM-1, separately. Conclusion. Both miR-16-5p and mIR-4299 are promising factors for early diagnosis of SI-AKI and dynamic evaluation of the efficacy on it.

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“…We found that plasma kynurenine was acutely regulated during evoked endotoxemia, suggestive of a role in acute inflammatory responses. Kynurenine has recently been reported to be upregulated during COVID-19 infection, further highlighting a potential role for kynurenine as a biomarker of inflammatory activation 26 .…”

Section: Discussionmentioning

confidence: 98%

The genetic architecture of plasma kynurenine includes cardiometabolic disease mechanisms associated with the SH2B3 gene

Bagheri

Wang

Shi

et al. 2021

Sci Rep

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Inflammation increases the risk of cardiometabolic disease. Delineating specific inflammatory pathways and biomarkers of their activity could identify the mechanistic underpinnings of the increased risk. Plasma levels of kynurenine, a metabolite involved in inflammation, associates with cardiometabolic disease risk. We used genetic approaches to identify inflammatory mechanisms associated with kynurenine variability and their relationship to cardiometabolic disease. We identified single-nucleotide polymorphisms (SNPs) previously associated with plasma kynurenine, including a missense-variant (rs3184504) in the inflammatory gene SH2B3/LNK. We examined the association between rs3184504 and plasma kynurenine in independent human samples, and measured kynurenine levels in SH2B3-knock-out mice and during human LPS-evoked endotoxemia. We conducted phenome scanning to identify clinical phenotypes associated with each kynurenine-related SNP and with a kynurenine polygenic score using the UK-Biobank (n = 456,422), BioVU (n = 62,303), and Electronic Medical Records and Genetics (n = 32,324) databases. The SH2B3 missense variant associated with plasma kynurenine levels and SH2B3−/− mice had significant tissue-specific differences in kynurenine levels.LPS, an acute inflammatory stimulus, increased plasma kynurenine in humans. Mendelian randomization showed increased waist-circumference, a marker of central obesity, associated with increased kynurenine, and increased kynurenine associated with C-reactive protein (CRP). We found 30 diagnoses associated (FDR q < 0.05) with the SH2B3 variant, but not with SNPs mapping to genes known to regulate tryptophan-kynurenine metabolism. Plasma kynurenine may be a biomarker of acute and chronic inflammation involving the SH2B3 pathways. Its regulation lies upstream of CRP, suggesting that kynurenine may be a biomarker of one inflammatory mechanism contributing to increased cardiometabolic disease risk.

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Identifying cell-enriched miRNAs in kidney injury and repair

Cited by 24 publications

References 61 publications

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

Evaluation Value of Serum miR-4299 and miR-16-5p in Risk Stratification of Sepsis-Induced Acute Kidney Injury

The genetic architecture of plasma kynurenine includes cardiometabolic disease mechanisms associated with the SH2B3 gene

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