Non-coding RNAs as potential biomarkers and therapeutic targets in polycystic kidney disease

Zheng, Qi; Reid, Glen; Eccles, Michael R.; Stayner, Cherie

doi:10.3389/fphys.2022.1006427

Cited by 10 publications

(8 citation statements)

References 68 publications

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“…Kidney cysts in mouse and human ADPKD have increased renal expressions of miR-17, which represses oxidative phosphorylation and FAO by inhibiting peroxisome proliferator-activated receptor alpha (PPARα), a regulator of lipid metabolism [ 58 ]. Mitochondrial fatty-acid β-oxidation (FAO) is reduced in cell lines derived from ADPKD mouse models and leads to increase fatty-acid biosynthesis [ 59 , 60 ].…”

Section: New Biomarkers In Adpkdmentioning

confidence: 99%

“…These findings indicate that the dysfunctional miRNA expression in the cystic epithelial cells is an indispensable factor in the development of PKD due to its multiple roles in disease pathogenesis: oxidative stress in mitochondrial metabolism, dysregulated cell proliferation, autophagy and apoptosis, inflammation, fibrosis, cell-to-cell contact via extracellular vesicles, and exosomes [ 59 , 80 ].…”

Section: New Biomarkers In Adpkdmentioning

confidence: 99%

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Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease—The Promised Land?

Pana,

Stanigut,

Cimpineanu

et al. 2023

Medicina

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, and it leads to end-stage renal disease (ESRD). The clinical manifestations of ADPKD are variable, with extreme differences observable in its progression, even among members of the same family with the same genetic mutation. In an age of new therapeutic options, it is important to identify patients with rapidly progressive evolution and the risk factors involved in the disease’s poor prognosis. As the pathophysiological mechanisms of the formation and growth of renal cysts have been clarified, new treatment options have been proposed to slow the progression to end-stage renal disease. Furthermore, in addition to the conventional factors (PKD1 mutation, hypertension, proteinuria, total kidney volume), increasing numbers of studies have recently identified new serum and urinary biomarkers of the disease’s progression, which are cheaper and more easily to dosing from the early stages of the disease. The present review discusses the utility of new biomarkers in the monitoring of the progress of ADPKD and their roles in new therapeutic approaches.

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Section: New Biomarkers In Adpkdmentioning

confidence: 99%

Section: New Biomarkers In Adpkdmentioning

confidence: 99%

Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease—The Promised Land?

Pana,

Stanigut,

Cimpineanu

et al. 2023

Medicina

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“…Studies have demonstrated the presence of altered extracellular vesicles profiles, in term of their nucleic acid and protein content, in various renal diseases including ADPKD 11,21 . The extracellular vesicles content, specifically small non‐coding RNAs, are considered to play a role in the pathogenesis of ADPKD by influencing various signaling pathways through the post‐transcriptional control of related genes 22 . The pathologically modified extracellular vesicles profiles may provide potential biomarkers for disease diagnosis, prognosis and monitoring.…”

Section: Introductionmentioning

confidence: 99%

“…11,21 The extracellular vesicles content, specifically small non-coding RNAs, are considered to play a role in the pathogenesis of ADPKD by influencing various signaling pathways through the post-transcriptional control of related genes. 22 The pathologically modified extracellular vesicles profiles may provide potential biomarkers for disease diagnosis, prognosis and monitoring.…”

Section: Introductionmentioning

confidence: 99%

Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease

Ali,

Malik,

Abu‐Farha

et al. 2024

The Journal of Gene Medicine

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BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease progressing to end‐stage renal disease. There is a pressing need for the identification of early ADPKD biomarkers to enable timely intervention and the development of effective therapeutic approaches. Here, we profiled human urinary extracellular vesicles small RNAs by small RNA sequencing in patients with ADPKD and compared their differential expression considering healthy control individuals to identify dysregulated small RNAs and analyze downstream interaction to gain insight about molecular pathophysiology.MethodsThis is a cross‐sectional study where urine samples were collected from a total of 23 PKD1‐ADPKD patients and 28 healthy individuals. Urinary extracellular vesicles were purified, and small RNA was isolated and sequenced. Differentially expressed Small RNA were identified and functional enrichment analysis of the critical miRNAs was performed to identify driver genes and affected pathways.ResultsmiR‐320b, miR‐320c, miR‐146a‐5p, miR‐199b‐3p, miR‐671‐5p, miR‐1246, miR‐8485, miR‐3656, has_piR_020497, has_piR_020496 and has_piR_016271 were significantly upregulated in ADPKD patient urine extracellular vesicles and miRNA‐29c was significantly downregulated. Five ‘driver’ target genes (FBRS, EDC3, FMNL3, CTNNBIP1 and KMT2A) were identified.ConclusionsThe findings of the present study make significant contributions to the understanding of ADPKD pathogenesis and to the identification of novel biomarkers and potential drug targets aimed at slowing disease progression in ADPKD.

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“…The genetic underpinnings of PLD suggest the presence of a primary pathogenic germline variant in a PLD gene, and a secondary pathogenic somatic variant [ 1 , 3 , 9 , 12 , 13 , 14 , 15 ]. The consequences of these variants involve many molecular pathways, and a wide range of factors have been suggested including (but not limited to) cAMP, estrogen, primary cilia dysfunction, bile acid levels, cell–matrix remodeling, epigenetics, post-translational modifications, autophagy, and aberrant proteostasis [ 2 , 3 , 8 , 9 , 10 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. This range of factors has resulted in a large variety in the potential targets for therapeutic treatment [ 2 , 3 , 8 , 9 , 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Novel α-1,3-Glucosyltransferase Variants and Their Broad Clinical Polycystic Liver Disease Spectrum

Boerrigter,

te Morsche,

Venselaar

et al. 2023

Genes

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Protein-truncating variants in α-1,3-glucosyltransferase (ALG8) are a risk factor for a mild cystic kidney disease phenotype. The association between these variants and liver cysts is limited. We aim to identify pathogenic ALG8 variants in our cohort of autosomal dominant polycystic liver disease (ADPLD) individuals. In order to fine-map the phenotypical spectrum of pathogenic ALG8 variant carriers, we performed targeted ALG8 screening in 478 ADPLD singletons, and exome sequencing in 48 singletons and 4 patients from two large ADPLD families. Eight novel and one previously reported pathogenic variant in ALG8 were discovered in sixteen patients. The ALG8 clinical phenotype ranges from mild to severe polycystic liver disease, and from innumerable small to multiple large hepatic cysts. The presence of <5 renal cysts that do not affect renal function is common in this population. Three-dimensional homology modeling demonstrated that six variants cause a truncated ALG8 protein with abnormal functioning, and one variant is predicted to destabilize ALG8. For the seventh variant, immunostaining of the liver tissue showed a complete loss of ALG8 in the cystic cells. ALG8-associated ADPLD has a broad clinical spectrum, including the possibility of developing a small number of renal cysts. This broadens the ADPLD genotype–phenotype spectrum and narrows the gap between liver-specific ADPLD and kidney-specific ADPKD.

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Non-coding RNAs as potential biomarkers and therapeutic targets in polycystic kidney disease

Cited by 10 publications

References 68 publications

Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease—The Promised Land?

Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease—The Promised Land?

Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease

Novel α-1,3-Glucosyltransferase Variants and Their Broad Clinical Polycystic Liver Disease Spectrum

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