Unique molecular profile of exosomes derived from primary human proximal tubular epithelial cells under diseased conditions

Wang, Xiangju, Wilkinson, Ray, Kildey, Katrina, Potriquet, Jeremy, Mulvenna, Jason, Lobb, Richard J., Möller, Andreas, Cloonan, Nicole, Mukhopadhyay, Pamela, Kassianos, Andrew J., and Healy, Helen (2017) Unique molecular profile of exosomes derived from primary human proximal tubular epithelial cells under diseased conditions. Journal of Extracellular Vesicles, 6 (1). 1314073.

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Human proximal tubular epithelial cells (PTEC) of the kidney are known to respond to and mediate the disease process in a wide range of kidney diseases, yet their exosomal production and exosome molecular cargo remain a mystery. Here we investigate, for the first time, the production and molecular content of exosomes derived from primary human PTEC cultured under normal and diseased conditions representing a spectrum of in vivo disease severity from early inflammation, experienced in multiple initial kidney disease states, through to hypoxia, frequently seen in late stage chronic kidney disease (CKD) due to fibrosis and vascular compromise. We demonstrate a rapid reproducible methodology for the purification of PTEC-derived exosomes, identify increased numbers of exosomes from disease-state cultures and identify differential expression levels of both known and unique miRNA and protein species from exosomes derived from different disease-culture conditions. The validity of our approach is supported by the identification of miRNA, proteins and pathways with known CKD associations, providing a rationale to further evaluate these novel and known pathways as targets for therapeutic intervention.

Item ID: 54244
Item Type: Article (Research - C1)
ISSN: 2001-3078
Keywords: human proximal tubular epithelial cells, exosomes, inflammation, hypoxia, microRNA
Additional Information:

© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: Pathology Queensland, Royal Brisbane and Women's Hospital, National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC Project Grant GNT1099222
Date Deposited: 21 Jun 2018 01:27
FoR Codes: 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310199 Biochemistry and cell biology not elsewhere classified @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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