Exosomal mitochondrial tRNAs and miRNAs as potential predictors of inflammation in renal proximal tubular epithelial cells

Exosomes have emerged as a valuable repository of novel biomarkers for human diseases such as chronic kidney disease (CKD). From a healthy control group, we performed microRNA (miRNA) profiling of urinary exosomes and compared it with a cell culture model of renal proximal tubular epithelial cells (...

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Vydáno v:Molecular therapy. Nucleic acids Ročník 28; s. 794 - 813
Hlavní autoři: Ranches, Glory, Zeidler, Maximilian, Kessler, Roman, Hoelzl, Martina, Hess, Michael W., Vosper, Jonathan, Perco, Paul, Schramek, Herbert, Kummer, Kai K., Kress, Michaela, Krogsdam, Anne, Rudnicki, Michael, Mayer, Gert, Huettenhofer, Alexander
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 14.06.2022
American Society of Gene & Cell Therapy
Elsevier
Témata:
biomarkers
chronic kidney disease
cytokines
exosomes
inflammation and fibrosis
miRNAs
MT: Oligonucleotides: Diagnostics and Biosensors
mtRNAs
ncRNAs
Original
renal proximal tubular epithelial cells
chronic kidney disease
miRNAs
MT: Oligonucleotides: Diagnostics and Biosensors
renal proximal tubular epithelial cells
exosomes
biomarkers
inflammation and fibrosis
cytokines
mtRNAs
ncRNAs
ISSN:2162-2531, 2162-2531
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Shrnutí:Exosomes have emerged as a valuable repository of novel biomarkers for human diseases such as chronic kidney disease (CKD). From a healthy control group, we performed microRNA (miRNA) profiling of urinary exosomes and compared it with a cell culture model of renal proximal tubular epithelial cells (RPTECs). Thereby, a large fraction of abundant urinary exosomal miRNAs could also be detected in exosomes derived from RPTECs, indicating them as a suitable model system for investigation of CKD. We subsequently analyzed exosomes from RPTECs in pro-inflammatory and pro-fibrotic states, mimicking some aspects of CKD. Following cytokine treatment, we observed a significant increase in exosome release and identified 30 dysregulated exosomal miRNAs, predominantly associated with the regulation of pro-inflammatory and pro-fibrotic-related pathways. In addition to miRNAs, we also identified 16 dysregulated exosomal mitochondrial RNAs, highlighting a pivotal role of mitochondria in sensing renal inflammation. Inhibitors of exosome biogenesis and release significantly altered the abundance of selected candidate miRNAs and mitochondrial RNAs, thus suggesting distinct sorting mechanisms of different non-coding RNA (ncRNA) species into exosomes. Hence, these two exosomal ncRNA species might be employed as potential indicators for predicting the pathogenesis of CKD and also might enable effective monitoring of the efficacy of CKD treatment. [Display omitted] Renal proximal tubular epithelial cells (RPTECs) play an important role in the initiation and progression of chronic kidney disease (CKD). By analysis of exosomes derived from an in vitro model of RPTECs, we identified specific exosomal miRNAs, as well as mitochondrial tRNAs, as potential biomarkers for early diagnosis of CKD.
Bibliografie:ObjectType-Article-1
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ISSN:2162-2531
2162-2531
DOI:10.1016/j.omtn.2022.04.035