Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury

Pavkovic, Mira; Riefke, Bjoern; Ellinger‐Ziegelbauer, Heidrun

doi:10.1016/j.tox.2014.05.005

Cited by 73 publications

(77 citation statements)

References 42 publications

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“…In particular, miR-18a-5p was associated with the acute response to kidney injury, miR-132-3p had moderate to high expression throughout the entire response to injury, and the highest expression of miR-146b-5p was observed during the later stages of injury and fibrosis. Interestingly, some of the miRNAs found to be differentially expressed in our study have also been shown to be significantly increased in the urine of rats treated with cisplatin, including miR-18a, which was upregulated at early time points following injury (days 5 and 8), and miR-146b, which was upregulated weeks after initiation of injury (days 15 and 26) (Pavkovic et al , 2014). This suggests that these miRNAs may have potential application as biomarkers in rodent models, although this would require additional investigation.…”

Section: Discussionmentioning

confidence: 57%

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

Pellegrini

Gerlach

Craciun

et al. 2016

Toxicology and Applied Pharmacology

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Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250 mg/kg i.p.) kidney injury and fibrosis. From the 103 miRNAs that were differentially expressed over the time course (>2-fold, p<0.05), we chose to further investigate miR-18a-5p, which is expressed during the acute stage of the injury; miR-132-3p, which is upregulated during transition between acute and fibrotic injury; and miR-146b-5p, which is highly expressed at the peak of fibrosis. Using qRT-PCR, we confirmed the increased expression of these candidate miRNAs in the folic acid model as well as in other established mouse models of acute injury (ischemia/reperfusion injury) and fibrosis (unilateral ureteral obstruction). In situ hybridization confirmed high expression of miR-18a-5p, miR-132-3p and miR-146b-5p throughout the kidney cortex in mice and humans with severe kidney injury or fibrosis. When primary human proximal tubular epithelial cells were treated with model nephrotoxicants such as cadmium chloride (CdCl2), arsenic trioxide, aristolochic acid (AA), potassium dichromate (K2Cr2O7) and cisplatin, miRNA-132-3p was upregulated 4.3-fold after AA treatment and 1.5-fold after K2Cr2O7 and CdCl2 treatment. These results demonstrate the application of temporal small RNA sequencing to identify miR-18a, miR-132 and miR-146b as differentially expressed miRNAs during distinct phases of kidney injury and fibrosis progression.

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Section: Discussionmentioning

confidence: 57%

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

Pellegrini

Gerlach

Craciun

et al. 2016

Toxicology and Applied Pharmacology

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“…More recently, Vaidya and colleagues (17) reported that cisplatin induced more severe AKI in miR-155-deficient mice, suggesting an important role of miR-155 in renoprotection. In addition, multiple microRNAs have been identified to correlate with the development of cisplatin nephrotoxicity and thus have the potential to be diagnostic biomarkers (18,19). Our current study initially examined the effect of overall depletion of microRNA by using the PTDicer KO mouse model (Fig.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375 Is Induced in Cisplatin Nephrotoxicity to Repress Hepatocyte Nuclear Factor 1-β

Hao

Lou

Wei

et al. 2017

Journal of Biological Chemistry

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Edited by Joel GottesfeldNephrotoxicity is a major adverse effect of cisplatin-mediated chemotherapy in cancer patients. The pathogenesis of cisplatininduced nephrotoxicity remains largely unclear, making it difficult to design effective renoprotective approaches. Here, we have examined the role of microRNAs (miRNAs) in cisplatininduced nephrotoxicity. We show that cisplatin nephrotoxicity was not affected by overall depletion of both beneficial and detrimental miRNAs from kidney proximal tubular cells in mice in which the miRNA-generating enzyme Dicer had been conditionally knocked out. To identify miRNAs involved in cisplatin nephrotoxicity, we used microarray analysis to profile miRNA expression and identified 47 up-regulated microRNAs and 20 down-regulated microRNAs in kidney cortical tissues. One upregulated miRNA was miR-375, whose expression was also induced in cisplatin-treated renal tubular cells. Interestingly, inhibition of miR-375 decreased cisplatin-induced apoptosis, suggesting that miR-375 is a cell-damaging or pro-apoptotic agent. Blockade of P53 or NF-B attenuated cisplatin-induced miR-375 expression, supporting a role of P53 and NF-B in miR-375 induction. We also identified hepatocyte nuclear factor 1 homeobox B (HNF-1␤) as a key downstream target of miR-375. Of note, we further demonstrated that HNF-1␤ protected renal cells against cisplatin-induced apoptosis. Together, these results suggest that upon cisplatin exposure, P53 and NF-B collaboratively induce miR-375 expression, which, in turn, represses HNF-1␤ activity, resulting in renal tubular cell apoptosis and nephrotoxicity.

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“…Although, extensive human studies are still required, initial steps have been taken to demonstrate the potential utility of miRNAs, especially in the urine, for assessing AKI. Multiple studies (90,96,104,113,124,155,159,160) in humans and animal models have identified specific miRNAs as potential diagnostic markers for the early detection of AKI. Such approaches would be of tremendous clinical value to prevent progression from AKI to renal failure.…”

Section: Acute Kidney Injurymentioning

confidence: 99%

Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases

Bhatt

Kato

Natarajan

2016

American Journal of Physiology-Renal Physiology

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MicroRNAs (miRNA) are endogenously produced short noncoding regulatory RNAs that can repress gene expression by posttranscriptional mechanisms. They can therefore influence both normal and pathological conditions in diverse biological systems. Several miRNAs have been detected in kidneys, where they have been found to be crucial for renal development and normal physiological functions as well as significant contributors to the pathogenesis of renal disorders such as diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and others, due to their effects on key genes involved in these disease processes. miRNAs have also emerged as novel biomarkers in these renal disorders. Due to increasing evidence of their actions in various kidney segments, in this mini-review we discuss the functional significance of altered miRNA expression during the development of renal pathologies and highlight emerging miRNA-based therapeutics and diagnostic strategies for early detection and treatment of kidney diseases.

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Urinary microRNA profiling for identification of biomarkers after cisplatin-induced kidney injury

Cited by 73 publications

References 42 publications

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

MicroRNA-375 Is Induced in Cisplatin Nephrotoxicity to Repress Hepatocyte Nuclear Factor 1-β

Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases

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