Extracellular vesicles in renal physiology and clinical applications for renal disease

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Abstract

Many cells in the nephron release extracellular vesicles (EVs). EVs envelop nucleic acids, proteins, and lipids. The surfaces of EVs express donor cell-specific markers, ligands, and major histocompatibility complex molecules. They are involved in cell-to-cell communication, immune modulation, and the removal of unwanted materials from cells. EVs have been studied as biomarkers of specific diseases and have potential therapeutic applications. Recent research has emphasized the functions of EVs in the kidney. This review provides an overview of recent findings related to the roles of EVs in the nephron, and their utility as biomarkers and therapeutic factors in renal disease.

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Most cited references 62

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Extracellular vesicle isolation and characterization: toward clinical application.

Rong Xu, David W. Greening, Hong-Jian Zhu … (2016)

Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.

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Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Akiko Takahashi, Ryo Okada, Koji Nagao … (2017)

Emerging evidence is revealing that exosomes contribute to many aspects of physiology and disease through intercellular communication. However, the biological roles of exosome secretion in exosome-secreting cells have remained largely unexplored. Here we show that exosome secretion plays a crucial role in maintaining cellular homeostasis in exosome-secreting cells. The inhibition of exosome secretion results in the accumulation of nuclear DNA in the cytoplasm, thereby causing the activation of cytoplasmic DNA sensing machinery. This event provokes the innate immune response, leading to reactive oxygen species (ROS)-dependent DNA damage response and thus induce senescence-like cell-cycle arrest or apoptosis in normal human cells. These results, in conjunction with observations that exosomes contain various lengths of chromosomal DNA fragments, indicate that exosome secretion maintains cellular homeostasis by removing harmful cytoplasmic DNA from cells. Together, these findings enhance our understanding of exosome biology, and provide valuable new insights into the control of cellular homeostasis.

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Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells.

Mario Squadrito, Caroline Baer, Frédéric X. Burdet … (2014)

MicroRNA (miRNA) transfer via exosomes may mediate cell-to-cell communication. Interestingly, specific miRNAs are enriched in exosomes in a cell-type-dependent fashion. However, the mechanisms whereby miRNAs are sorted to exosomes and the significance of miRNA transfer to acceptor cells are unclear. We used macrophages and endothelial cells (ECs) as a model of heterotypic cell communication in order to investigate both processes. RNA profiling of macrophages and their exosomes shows that miRNA sorting to exosomes is modulated by cell-activation-dependent changes of miRNA target levels in the producer cells. Genetically perturbing the expression of individual miRNAs or their targeted transcripts promotes bidirectional miRNA relocation from the cell cytoplasm/P bodies (sites of miRNA activity) to multivesicular bodies (sites of exosome biogenesis) and controls miRNA sorting to exosomes. Furthermore, the use of Dicer-deficient cells and reporter lentiviral vectors (LVs) for miRNA activity shows that exosomal miRNAs are transferred from macrophages to ECs to detectably repress targeted sequences. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Korean J Intern Med

Journal ID (iso-abbrev): Korean J. Intern. Med

Journal ID (publisher-id): KJIM

Title: The Korean Journal of Internal Medicine

Publisher: The Korean Association of Internal Medicine

ISSN (Print): 1226-3303

ISSN (Electronic): 2005-6648

Publication date (Print): May 2019

Publication date (Electronic): 30 April 2019

Volume: 34

Issue: 3

Pages: 470-479

Affiliations

Division of Nephrology, Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, Seoul, Korea

Author notes

Correspondence to Soon Hyo Kwon, M.D. Division of Nephrology, Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea Tel: +82-2-710-3274 Fax: +82-2-792-5812 E-mail: ksoonhyo@ 123456schmc.ac.kr

This paper was contributed by The Korean Society of Nephrology.

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Soon Hyo Kwon http://orcid.org/0000-0002-4114-4196

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Publisher ID: kjim-2019-108

DOI: 10.3904/kjim.2019.108

PMC ID: 6506725

PubMed ID: 31048657

SO-VID: 246da18b-2244-40d0-afee-76bcb4cacb06

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Extracellular vesicles in renal physiology and clinical applications for renal disease

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Most cited references 62

Extracellular vesicle isolation and characterization: toward clinical application.

Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells.

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