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

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 deri...

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Autores principales: Jeon, Jin Seok, Kim, Eunbit, Bae, Yun-Ui, Yang, Won Mi, Lee, Haekyung, Kim, Hyoungnae, Noh, Hyunjin, Han, Dong Cheol, Ryu, Seongho, Kwon, Soon Hyo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349539/
https://www.ncbi.nlm.nih.gov/pubmed/32517075
http://dx.doi.org/10.3390/cells9061409
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author Jeon, Jin Seok
Kim, Eunbit
Bae, Yun-Ui
Yang, Won Mi
Lee, Haekyung
Kim, Hyoungnae
Noh, Hyunjin
Han, Dong Cheol
Ryu, Seongho
Kwon, Soon Hyo
author_facet Jeon, Jin Seok
Kim, Eunbit
Bae, Yun-Ui
Yang, Won Mi
Lee, Haekyung
Kim, Hyoungnae
Noh, Hyunjin
Han, Dong Cheol
Ryu, Seongho
Kwon, Soon Hyo
author_sort Jeon, Jin Seok
collection PubMed
description 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.
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spelling pubmed-73495392020-07-14 microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells Jeon, Jin Seok Kim, Eunbit Bae, Yun-Ui Yang, Won Mi Lee, Haekyung Kim, Hyoungnae Noh, Hyunjin Han, Dong Cheol Ryu, Seongho Kwon, Soon Hyo Cells Article 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. MDPI 2020-06-05 /pmc/articles/PMC7349539/ /pubmed/32517075 http://dx.doi.org/10.3390/cells9061409 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jeon, Jin Seok
Kim, Eunbit
Bae, Yun-Ui
Yang, Won Mi
Lee, Haekyung
Kim, Hyoungnae
Noh, Hyunjin
Han, Dong Cheol
Ryu, Seongho
Kwon, Soon Hyo
microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
title microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
title_full microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
title_fullStr microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
title_full_unstemmed microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
title_short microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
title_sort microrna in extracellular vesicles released by damaged podocytes promote apoptosis of renal tubular epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349539/
https://www.ncbi.nlm.nih.gov/pubmed/32517075
http://dx.doi.org/10.3390/cells9061409
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