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Table 11 Transcriptomics studies in kidney diseases

From: Genomic approaches in the search for molecular biomarkers in chronic kidney disease

PMID

Author

Year

Sample

Patients

Ethnics

Methodology

Main findings

29642064

Zhou

2018

Gene expression microarray datasets retrieved from GEO repository

18 DKD/40 HC, 

26 HTN/44 HC, 

68 IgAN/44 HC, 

36 MGN/44 HC, 

35 FSGS/62 HC

–

Integrative bioinformatics analysis

Affymetrix U133 Plus 2.0 Affymetrix U133 A

Glomeruli: 176 genes were differentially expressed among all diseases, 104 upregulated (e.g., FCN1, CX3CR1) and 72 downregulated (e.g., APOM, SLC13A1). Gene Ontology analysis showed mainly cellular components associated with diseased glomeruli, as integral components of the plasma membrane, extracellular space, and within the MHC class II protein complex. Pathway enrichment analysis showed dysregulation of several metabolic, immune response, and signalling pathways (e.g., lipids/lipoproteins and amino acids metabolism, SLC-mediated transmembrane transport, and IFN-γ pathway). Protein interaction network identified a cluster mainly associated with platelet dysfunction, abnormal interleukin signalling, and extracellular matrix organization

Tubules: 50 genes were differentially expressed among all diseases, nine upregulated (e.g., COL3A1, MARCKS) and 41 downregulated (e.g., GDF15, RGS3). Gene Ontology analysis showed association mainly with molecule binding and transcription factor activity. Pathway enrichment analysis showed dysregulation of several signalling pathways (e.g., cholecystokinin receptor (CCKR), apoptosis, PI3 K-Akt, MAPK, and TGF-β signalling pathways). Protein interaction network identified a cluster mainly associated with SMAD2/SMAD3/SMAD4 heterotrimer-regulated transcription, TGF-β receptor complex signalling, and interleukin signalling

Nine genes were significantly differentially expressed both in diseased glomeruli and tubules (IFI16, COL3A1, ZFP36, NR4A3, DUSP1, FOSB, HBB, FN1, PTPRC)

28158872

Zhao

2017

CD4 + T Cells

15 SLE

15 HC

United States

qRT-PCR

TNFAIP3 expression has been found downregulated in CD4 + T cells from SLE

26986150

Zhai

2016

B lymphocytes

166 IgAN

77 HC

China

qRT-PCR

Increased TNFSF13 expression is accompanied by upregulation of its receptors in B-lymphocytes from IgAN patients, inducing Gd-IgA1 overproduction

26631632

Ju

2015

Biopsy

55 CKD

United States

Microarray

(Affymetrix GeneChip and TaqMan Low Density Arrays)

Urine levels of EGF correlated with tissue EGF transcript expression and predicted eGFR

26490557

Leal

2015

Peripheral

Blood mononuclear

cells

20 CKD

20 HD

11 HC

Brazil

qRT-PCR

NFE2L2 mRNA was positively correlated with NF-κB mRNA expression in CKD patients (r = 0.52, p = 0.02) and healthy individuals

26116588

Perlman

2015

Blood

20 T2DM + DKD, 

20 HC

United States

qRT-PCR

transcripts levels differentially expressed in T2DM with nephropathy

elevated expression occurred in early stage 1-2, before a significant decline in eGFR

Interest in MCP-1, FGF-2, VEGF and EGF

23921255

Hara

2013

Leukocytes

40 CKD

20 HC

Japan

qRT-PCR

S100A12 expression was significantly higher in CKD patients compared to healthy controls

24347824

Yadav

2013

CD4+CD28null peripheral mononuclear cells

25 CKD

8 HC

India

qRT-PCR

Basal expression of IFN-γ, perforin, and granzyme B in CD4+CD28null cells was increased in CKD

23061738

Chen

2012

Urine

35 CKD

12 HC

China

qRT-PCR

CTGF and NOV genes were overexpressed in CKD

21906921

Spoto

2012

Plasma

75 CKD

33 HC

Italy

qRT-PCR

Upregulation of TNF-α was inversely correlated with eGFR

Increase of plasma IL-6 in early stages of CKD, without showing any further increase at more severe stages

23024773

Rudnicki

2012

Biopsy

3 DKD

7 HTN

19 IgAN

10 MCD

7 FSGS

8 MGN

2 LN

2 MPGN

1 RPGN

16 Other

Switzerland

Microarray analysis

Correlation of versican isoforms V0 and V1 with creatinine levels

22969957

Tachaudomdach

2012

Biopsy

39 LN

Thailand

qRT-PCR

TGF-β1 and collagen I were correlated with CTGF expression

Baseline eGFR and Renal CTGF mRNA expression were inversely correlated

20650904

Brabcova

2011

Biopsy

51 IgAN

Czech Republic

qRT-PCR

Higher TGF-β1 expression associated with IgAN progression

21640098

Chon

2011

Leukocytes

20 CKD

10 HC

Netherlands

qRT-PCR

Inverse correlation of leukocyte angiotensin II AT1 receptor mRNA expression with renal function

Leukocyte angiotensin II AT1 receptor expression is higher in CKD

21040163

Lepenies

2010

Biopsy

64 CKD

UK

qRT-PCR

Inverse correlation of mRNA expression of peroxisome proliferator-activated receptor gamma (PPARγ) with renal function

19698090

Granata

2009

Peripheral blood mononuclear cells

9 CKD II-III,

17 HD, 

8 HC

Helsinki

Microarray analysis

COX6C, COX7C, ATP5ME, and UQCRH were all significantly higher in CKD IV-V compared to CKD II-III and HC

18758661

Ibrahim

2008

Biopsy

20 T2DM, 

4 normal tissue from renal tumor patients

Egyptian

qRT-PCR

Increased PKC alpha gene expression in diabetic patients with CKD

PKC alpha gene concentrations and proteinuria had significant correlation in diabetic patients. 

18784644

Zehnder

2008

Urine

174 CKD

81.6% white, 10.9% Asian, 6.9% Afro-Caribbean

qRT-PCR

MCP-1 expression was increased in those with acute renal inflammation

16564935

Szeto

2006

Urine

131 CKD

China

qRT-PCR

Urinary HGF expression remained an independent predictor of the primary end point, it was increased in those at risk of end point.

15561743

Szeto

2005

Urine

29 CKD

10 HC

China

qRT-PCR

Overexpression of TGF-β and MCP-1 was associated with glomerulosclerosis

Overexpression of collagen IV was associated with CKD

  1. Akt: Protein kinase B, also known as Akt; APOM: apolipoprotein M; AT1: angiotensin II Type 1 receptor; ATP5ME: ATP synthase membrane subunit e; CCKR: cholecystokinin receptor; CD4: cluster of differentiation 4; CD28: cluster of differentiation 28; CKD: chronic kidney disease; COL3A1: collagen type III alpha 1 chain; COX6C: cytochrome c oxidase subunit 6C; COX7C: cytochrome c oxidase subunit 7C; CTGF: connective tissue growth factor; CX3CR1: C-X3-C motif chemokine receptor 1; DKD: diabetic kidney disease; DUSP1: dual specificity phosphatase 1; EGF: epidermal growth factor; eGFR: estimated glomerular filtration rate; FCN1: ficolin 1; FGF: fibroblast growth factor; FN1: fibronectin 1; FOSB: FosB proto-oncogene; AP-1 transcription factor subunit; FSGS: focal segmental glomerulosclerosis; Gd-IgA1: galactose-deficient hinge region O-glycans; GDF15: growth differentiation factor 15; GEO: gene expression omnibus;, HBB: hemoglobin subunit beta; HC: healthy controls; HD: hemodialysis; HGF hepatocyte growth factor; HTN: hypertension; IFI16: interferon gamma inducible protein 16; IFN-γ: interferon gamma; IgAN: IgA nephropathy; IL-6: interleukin 6; LN: lupus nephritis; MAPK: Mitogen-activated protein kinases; MARCKS: myristoylated alanine rich protein kinase C substrate; MCD: minimal change disease; MHC: major histocompatibility complex; MCP-1: monocyte Chemoattractant Protein-1; MGN: membranous nephropathy; MPGN: membranoproliferative glomerulonephritis; mRNA: messenger ribonucleic acid; NF-κB: NF-kappa B complex subunits; NFE2L2: nuclear factor, erythroid 2 like 2; NOV: nephroblastoma overexpressed; NR4A3: nuclear receptor subfamily 4 group A member 3; PKC: protein kinase C; PPARγ: peroxisome proliferator-activated receptor gamma; PTPRC: protein tyrosine phosphatase, receptor type C; PI3K: phosphatidylinositol-3-kinases; qRT-PCR: quantitative reverse transcription polymerase chain reaction; RGS3: regulator of G protein signalling 3; RPGN: rapidly progressive glomerulonephritis; S100A12: S100 calcium binding protein A12; SLC: human solute carrier gene superfamily; SLC13A1: solute carrier family 13 member 1; SLE: systematic lupus erythematosus; SMAD2: SMAD family member 2; SMAD3: SMAD family member 3; SMAD4: SMAD family member 4; T1DM: type 1 diabetes mellitus; T2DM: type 2 diabetes mellitus; TNF: tumour necrosis factor superfamily; TGF-β1: transforming growth factor beta 1; TNF-α: tumour necrosis factor alpha; TNFAIP3: TNF alpha induced protein 3; TNFSF13: TNF superfamily member 13; TGF-β: transforming growth factor beta; UK: United Kingdom; UQCRH: ubiquinol-cytochrome c reductase hinge protein; VEGF: vascular endothelial growth factor; ZFP36: ZFP36 ring finger protein