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

Dwivedi, Om Prakash (author)
University of Helsinki
Barreiro, Karina (author)
University of Helsinki
Käräjämäki, Annemari (author)
Vaasa Health Care Center
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Valo, Erkka (author)
Folkhälsan Research Center
Giri, Anil K. (author)
University of Helsinki
Prasad, Rashmi B. (author)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
Roy, Rishi Das (author)
University of Helsinki
Thorn, Lena M. (author)
Folkhälsan Research Center
Rannikko, Antti (author)
University of Helsinki
Holthöfer, Harry (author)
University of Helsinki
Gooding, Kim M. (author)
University of Exeter
Sourbron, Steven (author)
Delic, Denis (author)
Gomez, Maria F. (author)
Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
Groop, Per-Henrik (author)
Tuomi, Tiinamaija (author)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Helsinki University Central Hospital,University of Helsinki,Folkhälsan Research Center
Forsblom, Carol (author)
Groop, Leif (author)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki
Puhka, Maija (author)
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 (creator_code:org_t)
2023
2023
English.
In: iScience. - 2589-0042. ; 26:5
Related links:
http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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