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  • Dwivedi, Om PrakashUniversity of Helsinki (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

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  • LIBRIS-ID:oai:lup.lub.lu.se:65011b76-a279-4b40-8e82-3ef0bcbaf801
  • https://lup.lub.lu.se/record/65011b76-a279-4b40-8e82-3ef0bcbaf801URI
  • https://doi.org/10.1016/j.isci.2023.106686DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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  • Barreiro, KarinaUniversity of Helsinki (author)
  • Käräjämäki, AnnemariVaasa Health Care Center (author)
  • Valo, ErkkaFolkhälsan Research Center (author)
  • Giri, Anil K.University of Helsinki (author)
  • Prasad, Rashmi B.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-rpa (author)
  • Roy, Rishi DasUniversity of Helsinki (author)
  • Thorn, Lena M.Folkhälsan Research Center (author)
  • Rannikko, AnttiUniversity of Helsinki (author)
  • Holthöfer, HarryUniversity of Helsinki (author)
  • Gooding, Kim M.University of Exeter (author)
  • Sourbron, Steven (author)
  • Delic, Denis (author)
  • Gomez, Maria F.Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups(Swepub:lu)mphy-mgo (author)
  • Groop, Per-Henrik (author)
  • Tuomi, TiinamaijaLund 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(Swepub:lu)ti8736tu (author)
  • Forsblom, Carol (author)
  • Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki(Swepub:lu)endo-lgr (author)
  • Puhka, Maija (author)
  • University of HelsinkiVaasa Health Care Center (creator_code:org_t)

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