Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Genome-wide mRNA profiling in urinary extracellular vesicles reveals stress gene signature for diabetic kidney disease

Dwivedi, Om Prakash ; Barreiro, Karina ; Käräjämäki, Annemari ; Valo, Erkka ; Giri, Anil K. ; Prasad, Rashmi B. LU ; Roy, Rishi Das ; Thorn, Lena M. ; Rannikko, Antti and Holthöfer, Harry , et al. (2023) In iScience 26(5).
Abstract
Urinary extracellular vesicles (uEV) are a largely unexplored source of kidney-derived mRNAs with potential to serve as a liquid kidney biopsy. We assessed ∼200 uEV mRNA samples from clinical studies by genome-wide sequencing to discover mechanisms and candidate biomarkers of diabetic kidney disease (DKD) in Type 1 diabetes (T1D) with replication in Type 1 and 2 diabetes. Sequencing reproducibly showed >10,000 mRNAs with similarity to kidney transcriptome. T1D DKD groups showed 13 upregulated genes prevalently expressed in proximal tubules, correlated with hyperglycemia and involved in cellular/oxidative stress homeostasis. We used six of them (GPX3, NOX4, MSRB, MSRA, HRSP12 and CRYAB) to construct a transcriptional “stress score” that... (More)
Urinary extracellular vesicles (uEV) are a largely unexplored source of kidney-derived mRNAs with potential to serve as a liquid kidney biopsy. We assessed ∼200 uEV mRNA samples from clinical studies by genome-wide sequencing to discover mechanisms and candidate biomarkers of diabetic kidney disease (DKD) in Type 1 diabetes (T1D) with replication in Type 1 and 2 diabetes. Sequencing reproducibly showed >10,000 mRNAs with similarity to kidney transcriptome. T1D DKD groups showed 13 upregulated genes prevalently expressed in proximal tubules, correlated with hyperglycemia and involved in cellular/oxidative stress homeostasis. We used six of them (GPX3, NOX4, MSRB, MSRA, HRSP12 and CRYAB) to construct a transcriptional “stress score” that reflected long-term decline of kidney function and could even identify normoalbuminuric individuals showing early decline. We thus provide workflow and web-resource for studying uEV transcriptomes in clinical urine samples and stress-linked DKD markers as potential early non-invasive biomarkers or drug targets. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
iScience
volume
26
issue
5
article number
106686
publisher
Elsevier
external identifiers
  • scopus:85156240018
  • pmid:37216114
ISSN
2589-0042
DOI
10.1016/j.isci.2023.106686
language
English
LU publication?
yes
id
65011b76-a279-4b40-8e82-3ef0bcbaf801
date added to LUP
2023-05-03 10:42:51
date last changed
2024-05-03 22:24:48
@article{65011b76-a279-4b40-8e82-3ef0bcbaf801,
  abstract     = {{Urinary extracellular vesicles (uEV) are a largely unexplored source of kidney-derived mRNAs with potential to serve as a liquid kidney biopsy. We assessed ∼200 uEV mRNA samples from clinical studies by genome-wide sequencing to discover mechanisms and candidate biomarkers of diabetic kidney disease (DKD) in Type 1 diabetes (T1D) with replication in Type 1 and 2 diabetes. Sequencing reproducibly showed >10,000 mRNAs with similarity to kidney transcriptome. T1D DKD groups showed 13 upregulated genes prevalently expressed in proximal tubules, correlated with hyperglycemia and involved in cellular/oxidative stress homeostasis. We used six of them (GPX3, NOX4, MSRB, MSRA, HRSP12 and CRYAB) to construct a transcriptional “stress score” that reflected long-term decline of kidney function and could even identify normoalbuminuric individuals showing early decline. We thus provide workflow and web-resource for studying uEV transcriptomes in clinical urine samples and stress-linked DKD markers as potential early non-invasive biomarkers or drug targets.}},
  author       = {{Dwivedi, Om Prakash and Barreiro, Karina and Käräjämäki, Annemari and Valo, Erkka and Giri, Anil K. and Prasad, Rashmi B. and Roy, Rishi Das and Thorn, Lena M. and Rannikko, Antti and Holthöfer, Harry and Gooding, Kim M. and Sourbron, Steven and Delic, Denis and Gomez, Maria F. and Groop, Per-Henrik and Tuomi, Tiinamaija and Forsblom, Carol and Groop, Leif and Puhka, Maija}},
  issn         = {{2589-0042}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Genome-wide mRNA profiling in urinary extracellular vesicles reveals stress gene signature for diabetic kidney disease}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2023.106686}},
  doi          = {{10.1016/j.isci.2023.106686}},
  volume       = {{26}},
  year         = {{2023}},
}