Dataset Information

MicroRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells.

ABSTRACT: Tubular injury and fibrosis are associated with progressive kidney dysfunction in advanced glomerular disease. Glomerulotubular crosstalk is thought to contribute to tubular injury. microRNAs (miRNAs) in extracellular vesicles (EVs) can modulate distant cells. We hypothesized that miRNAs in EVs derived from injured podocytes lead to tubular epithelial cell damage. As proof of this concept, tubular epithelial (HK2) cells were cultured with exosomes from puromycin-treated or healthy human podocytes, and damage was assessed. Sequencing analysis revealed the miRNA repertoire of podocyte EVs. RNA sequencing identified 63 upregulated miRNAs in EVs from puromycin-treated podocytes. Among them, five miRNAs (miR-149, -424, -542, -582, and -874) were selected as candidates for inducing tubular apoptosis according to a literature-based search. To validate the effect of the miRNAs, HK2 cells were treated with miRNA mimics. EVs from injured podocytes induced apoptosis and p38 phosphorylation of HK2 cells. The miRNA-424 and 149 mimics led to apoptosis of HK2 cells. These results show that miRNAs in EVs from injured podocytes lead to damage to tubular epithelial cells, which may contribute to the development of tubular injury in glomerular disease.

SUBMITTER: Jeon JS

PROVIDER: S-EPMC7349539 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells.

Jeon Jin Seok JS Kim Eunbit E Bae Yun-Ui YU Yang Won Mi WM Lee Haekyung H Kim Hyoungnae H Noh Hyunjin H Han Dong Cheol DC Ryu Seongho S Kwon Soon Hyo SH

Cells 20200605 6

Tubular injury and fibrosis are associated with progressive kidney dysfunction in advanced glomerular disease. Glomerulotubular crosstalk is thought to contribute to tubular injury. microRNAs (miRNAs) in extracellular vesicles (EVs) can modulate distant cells. We hypothesized that miRNAs in EVs derived from injured podocytes lead to tubular epithelial cell damage. As proof of this concept, tubular epithelial (HK2) cells were cultured with exosomes from puromycin-treated or healthy human podocyte ...[more]

PMID: 32517075

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Project description:As any other radial glia in the central nervous system, Müller glia derive from the same neuroepithelial precursors, perform similar functions and exhibit neurogenic properties as radial glia in the brain. Müller glial cells retain progenitor-like characteristics in the adult human eye, and can partially restore visual function upon intravitreal transplantation into animal models of glaucoma. Recently, it has been demonstrated that intracellular communication is possible via the secretion of nano-sized membrane-bound extracellular vesicles (EV), which contain bioactive molecules like microRNA (miRNA) and proteins that induce phenotypic changes when internalised by recipient cells. We conducted high-throughput sequencing to profile the microRNA signature of EV populations secreted by Müller glia in culture, and used bioinformatic tools to evaluate their potential role in the neuroprotective signalling attributed to these cells. Sequencing of miRNA within Müller EV suggested enrichment with species associated with stem cells such as miR-21 and miR-16, as well as with miRNA previously found to play a role in diverse Müller cell functions in the retina: miR-9, miR-125b and the let-7 family. A total of 51 miRNA were found to be differentially enriched in EV compared to whole cells from which EV originated. Bioinformatic analyses also indicated preferential enrichment of species demonstrated to regulate genes involved in cell proliferation and survival, including PTEN the master inhibitor of the PI3K/AKT pathway. The results suggest that the release by Müller cells of miRNA-enriched EV abundant in species that regulate anti-apoptotic signalling networks, is likely to represent a significant proportion of the neuroprotective effect observed after transplantation of these cells into animal models of retinal ganglion cell (RGC)-depletion. Future work will seek to evaluate the modulation of putative genes, as well as the activation of these pathways in in vitro and in vivo models following the internalisation of Müller-EV by target retinal neurons.

Dataset Information

MicroRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells.

Publications

microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells.

Similar Datasets

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