Open AccessUnique molecular profile of exosomes derived from primary human proximal tubular epithelial cells under diseased conditions
Author(s) -
Wang Xiangju,
Wilkinson Ray,
Kildey Katrina,
Potriquet Jeremy,
Mulvenna Jason,
Lobb Richard J.,
Möller Andreas,
Cloonan Nicole,
Mukhopadhyay Pamela,
Kassianos Andrew J.,
Healy Helen
Publication year - 2017
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1080/20013078.2017.1314073
Subject(s) - microvesicles , exosome , kidney disease , inflammation , biology , kidney , disease , microrna , microbiology and biotechnology , immunology , cancer research , medicine , bioinformatics , pathology , gene , endocrinology , genetics
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.