University of Oulu

Mirja Krause, Aleksandra Rak-Raszewska, Florence Naillat, Ulla Saarela, Christina Schmidt, Veli-Pekka Ronkainen, Geneviève Bart, Seppo Ylä-Herttuala & Seppo J. Vainio (2018) Exosomes as secondary inductive signals involved in kidney organogenesis, Journal of Extracellular Vesicles, 7:1, 1422675, DOI: 10.1080/20013078.2017.1422675

Exosomes as secondary inductive signals involved in kidney organogenesis

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Author: Krause, Mirja1,2; Rak-Raszewska, Aleksandra1; Naillat, Florence1;
Organizations: 1Biocenter Oulu, Laboratory of Developmental Biology, InfoTech Oulu, Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2The Ritchie Centre, Hudson Institute of Medical Research Core, Clayton, Australia
3Biocenter Oulu, Tissue Imaging Center, Light Microscopy Facility, Faculty of Biochemistry and Molecular Medicine, Developmental Biology Lab, University of Oulu, Oulu, Finland
4Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.6 MB)
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Language: English
Published: Informa, 2018
Publish Date: 2018-04-16


The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also between tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species and proteins implicated in kidney development, exosomes are putative candidates to serve as developmental programming units in embryonic induction and tissue interactions. We used the mammalian metanephric kidney and its nephron-forming mesenchyme containing the nephron progenitor/stem cells as a model to investigate if secreted exosomes could serve as a novel type of inductive signal in a process defined as embryonic induction that controls organogenesis. As judged by several characteristic criteria, exosomes were enriched and purified from a cell line derived from embryonic kidney ureteric bud (UB) and from primary embryonic kidney UB cells, respectively. The cargo of the UB-derived exosomes was analysed by qPCR and proteomics. Several miRNA species that play a role in Wnt pathways and enrichment of proteins involved in pathways regulating the organization of the extracellular matrix as well as tissue homeostasis were identified. When labelled with fluorescent dyes, the uptake of the exosomes by metanephric mesenchyme (MM) cells and the transfer of their cargo to the cells can be observed. Closer inspection revealed that besides entering the cytoplasm, the exosomes were competent to also reach the nucleus. Furthermore, fluorescently labelled exosomal RNA enters into the cytoplasm of the MM cells. Exposure of the embryonic kidney-derived exosomes to the whole MM in an ex vivo organ culture setting did not lead to an induction of nephrogenesis but had an impact on the overall organization of the tissue. We conclude that the exosomes provide a novel signalling system with an apparent role in secondary embryonic induction regulating organogenesis.

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Series: Journal of extracellular vesicles
ISSN: 2001-3078
ISSN-E: 2001-3078
ISSN-L: 2001-3078
Volume: 7
Article number: 1422675
DOI: 10.1080/20013078.2017.1422675
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was supported by the Academy of Finland (206038, 121647, 250900, 260056, 2430265123 (Profi3)), Centre of Excellence grant 2012–2017 of the Academy of Finland (251314), the Sigrid Jusélius Foundation, the European Community’s Seventh Framework Programme FP7/2009 under grant agreement 305608 (EURenOmics: European Consortium for High-Throughput Research in Rare Kidney Diseases), Tekes BioRealHealth (24302443) and Finnish Cultural Foundation (personal grant to AR)
EU Grant Number: (305608) EURENOMICS - European Consortium for High-Throughput Research in Rare Kidney Diseases
Academy of Finland Grant Number: 121647
Detailed Information: 121647 (Academy of Finland Funding decision)
250900 (Academy of Finland Funding decision)
260056 (Academy of Finland Funding decision)
251314 (Academy of Finland Funding decision)
Copyright information: © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.