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

被引：11

作者：

Dwivedi, Om Prakash ^{[1
,2
]}

Barreiro, Karina ^{[1
]}

Karajamaki, Annemari ^{[2
,3
]}

Valo, Erkka ^{[3
,4
,5
]}

Giri, Anil K. ^{[8
,9
,10
]}

Prasad, Rashmi B. ^{[11
,12
]}

Roy, Rishi Das ^{[13
]}

Thorn, Lena M. ^{[4
,5
,6
,7
]}

Rannikko, Antti ^{[14
,15
,16
]}

Holthoefer, Harry ^{[17
]}

Gooding, Kim M. ^{[18
]}

Sourbron, Steven ^{[19
]}

Delic, Denis ^{[20
,21
]}

Gomez, Maria F. ^{[11
]}

Groop, Per-Henrik

Tuomi, Tiinamaija ^{[4
,12
,22
]}

Forsblom, Carol ^{[4
,5
,7
]}

Groop, Leif ^{[12
]}

Puhka, Maija ^{[1
]}

机构：

[1] Univ Helsinki, Inst Mol Med Finland FIMM, HiLIFE, Helsinki, Finland

[2] Univ Helsinki, Inst Mol Med Finland, FIMM EV & HiPrep Core, Helsinki, Finland

[3] Vaasa Cent Hosp, Dept Primary Hlth Care, Hietalahdenkatu 2-4, Vaasa 65130, Finland

[4] Vaasa Hlth Care Ctr, Diabet Ctr, Sepankylantie 14-16, Vaasa 65100, Finland

[5] Folkhalsan Inst Genet, Folkhalsan Res Ctr, Helsinki, Finland

[6] Univ Helsinki, Helsinki Univ Hosp, Dept Nephrol, Helsinki, Finland

[7] Helsinki Univ Hosp, Helsinki, Finland

[8] Univ Helsinki, Fac Med, Res Program Clin & Mol Metab, Helsinki, Finland

[9] Fdn Finnish Canc Inst FCI, Tukholmankatu 8, Helsinki 00290, Finland

[10] Univ Helsinki, iCAN Digital Precis Canc Med Flagship, Helsinki, Finland

[11] Univ Helsinki, HiLIFE Helsinki Inst Life Sci, Helsinki, Finland

[12] Lund Univ, Diabet Ctr, Dept Clin Sci, SE-21428 Malmo, Sweden

[13] Univ Helsinki, Inst Biotechnol, Helsinki, Finland

[14] Univ Helsinki, Fac Med, Res Program Syst Oncol, Helsinki 00014, Finland

[15] Univ Helsinki, Dept Urol, Helsinki 00014, Finland

[16] Helsinki Univ Hosp, Helsinki 00100, Finland

[17] Univ Med Ctr Hamburg Eppendorf, Dept Med, Hamburg, Germany

[18] Univ Exeter, Med Sch, Natl Inst Hlth Res Exeter Clin Res Facil, Diabet & Vasc Res Ctr, Exeter, England

[19] Univ Sheffield, Dept Imaging Infect Immun & Cardiovasc Dis, Sheffield, England

[20] Boehringer Ingelheim Pharm GmbH & Co KG, Biberach, Germany

[21] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med Nephrol Endocrinol Rheumatol Pneumol 5, Heidelberg, Germany

[22] Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland

来源：

ISCIENCE | 2023年 / 26卷 / 05期

基金：

欧盟地平线“2020”; 芬兰科学院; 瑞典研究理事会;

关键词：

NUCLEIC-ACIDS; NEPHROPATHY; DIAGNOSIS; TUBULE;

D O I：

10.1016/j.isci.2023.106686

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Urinary extracellular vesicles (uEV) are a largely unexplored source of kidney -derived mRNAs with potential to serve as a liquid kidney biopsy. We assessed X200 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 tran-scriptome. T1D DKD groups showed 13 upregulated genes prevalently ex-pressed 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 nor-moalbuminuric 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.

引用

页数：25

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