Table 1.
Transcriptomic profile in frozen whole renal tissue, FFPE renal tissue, and in isolated glomeruli and tubule-interstitium
| Authors | Year | Methodology | Renal tissue | DEGs | Main findings |
|---|---|---|---|---|---|
| Whole renal tissue | |||||
| Yano et al. | 2002 | HD cDNA microarray hybridization | OCT-Frozen | ↑ MAPK1, CRC protein, PTDSS, HLA-E, PLEK P47, FAP, ANXA4, MUC18, ELN, DHFR, KRAS, RBR107, PFKM, PLD, GRM, ZNF33A | Different gene profiles related to different grades of renal damage |
| Waga et al. | 2003 | Restriction endonucleolytic | OCT-Frozen | ↑ EST22972, MBP45K, GN01, EST22360, ubiquitin, gp330, prolyl2, E4TF1-47, CathD, Zinc29in4628, PDI, EST43719, OSF2 | Megalin may be a potential drug receptor |
| Lepenies et al. | 2010 | qRT-PCR | Frozen | ↑ PPARγ, IL-6, TGFβ-1, MCP-1 | PPARγ increases with loss of the renal function |
| Lepenies et al. | 2011 | qRT-PCR | Frozen | ↑ TLR4, MCP-1, TGFβ-1, IL-6 | TLR4 may be a significant mediator of inflammation and fibrotic renal injury |
| Brabcova et al. | 2011 | qRT-PCR | Frozen | ↑ CCL2, CCL5, TGFβ-1, HGF, BMP7 | TGFβ-1 is associated with advanced vasculopathy and fibrogenesis |
| Rudnicki et al. | 2012 | qRT-PCR | OCT-Frozen | ↑ Versican, TGFβ-1 | Versican increases the renal disease progression |
| Cox et al. | 2020 | Microarrays | FFPE | ↑ DEFA4, TNFAIP6, FAR2, LTB, CXCL6, ITGAX |
TNFAIP6 (active renal tissue); CXCL6 (chronic renal tissue) |
| Microdissected glomeruli and tubule-interstitium | |||||
| Liu et al. | 2017 | Microarray | G-TI | 25 differentially expressed pathways from microarray data | Gene profile in mesangial cells |
| Ebefors et al. | 2011 | Microarray | G-TI |
Glomeruli ↑ Biglycan, Decorin, Perlecan, NDST1, TGF-β1 Tubules ↓ Perlecan, VEGF |
Increased expression of perlecan indicates better outcome |
| Tao et al. | 2020 | Microarray | G | ↑ IFNG, pSTAT1, STAT, JAK1 | JAK-STAT signaling pathway |
| Hodgin et al. | 2014 | Microarray | G | ↑ AURKB, C1QA, C1QB, C2, CD163, CD44, CORO1C, FOXM1, GPR183, HPSE, KIF15, LAIR1, LAPTM5, LHFPL2, MAN2B1, MERTK, MS4A6A, PRC1, SLC43A3, TIMP1, VSIG4 | Innate immune response, activation of the classical complement pathway, matrix degradation and turnover, macrophage polarization |
| Ju et al. | 2009 | Microarray | G-TI | NCF2, MPV17I, S100A6, BGN, COL6A1, ITGB5, SLC13A3, DKK3 | Gene expression signature that predicts progressive renal fibrosis and CKD |
| Eikmans et al. | 2003 | qRT-PCR | G-TI |
Glomeruli ↑ TGF-β, collagen I, collagen IV, fibronectin Tubules ↑ TGF-β |
TGFβ may be a promising biomarker of renal outcome |
| Rudnicki et al. | 2007 | Microarray | TI |
↓ TIMP1, DUSP5; ↓ BIK, TAX1BP1, TIA1 (apoptosis); ↑ BMP7, DEFB1, RAB4A (cell differentiation); ↑ THBS3, ADAM22 (cell adhesion and differentiation); ↑ IGF1, CDC34, ANXA13, RRAS, MARK3 (cell proliferation and cell cycle control); ↑ DEFB1, IFNGR1, C1QR1, SERP1, TPST1 (immune response); ↑ RAB4A, RAB43, SNX2, SEC6L1, SEC14C1, TOMM7 (intracellular transport); ↑ TCN1, KCND3, AQP2, AQP4 (membrane transport); ↑ PTPN1, ROS1, PRKD3, HSPC121, CSNK1D, COPS6, NMU, FRAT1 (signal transduction) |
Proteinuria is associated to injury and repair mechanism |
| Reich et al. | 2010 | Microarray | TI | ↑ COL1A1, EGR1, ELF3, IER3, HBEGF, MAFF, MCL1, SAMD4A, PAI-1, STEAP1, TYMS | Proteinuria signature at tubular level, apoptosis of tubular cells, cell-to-cell signaling, cell cycle, renal fibrosis |
| Ju et al. | 2015 | Microarray | TI | ↑ NNMT, EGF, TMSB10, TIMP1, TUBA1A, ANXA1 | Prediction of kidney function |
| Shved et al. | 2017 | Microarray | G-TI |
↑ ABCG2, MXI1, NDRG1, RORA, VEGFA, BNIP3; ↓ BHLHE41, CXCR4, EDN1, HIF1A, ITGB2, MCL1, MET, PFKFB3 |
HIF-target genes correlated with renal function |
ABCG2, ATP binding cassette subfamily G member 2; ADAM22, A Disintegrin And Metalloproteinase domain 22; ANXA1, Annexin A1; ANXA4, Annexin A4; ANXA13, Annexin A13; AQP2, Aquaporin 2; AQP4, Aquaporin 4; AURKB, Aurora Kinase B; BGN, Biglycan; BHLHE41, Basic Helix-Loop-Helix Family Member E41; BIK, BCL2-interacting killer (apoptosis inducing); BNIP3, BCL2/Adenovirus E1B 19 kDa Interacting Protein 3; BMP7, Bone Morphogenic Protein-7; C1QA, Complement C1q A Chain; C1QB, Complement C1q B Chain; C1QR1, Complement component 1, q subcomponent, and receptor 1; C2, Complement 2; CATHD, Cathepsin D; CCL2, C–C motif chemokine ligand 2; CCL5, C–C motif chemokine ligand 5; CD44, CD44 molecule; CD163, CD163 molecule; CDC34, Cell division cycle 34; CKD, Chronic Kidney Disease; COL1A1, Collagen Type I Alpha 1 chain; COL6A1, Collagen type VI, α1; COPS6, COP9 constitutive photomorphogenic homolog subunit 6; CORO1C, Coronin 1C; CRC protein, Colorectal cancer protein; CSNK1D, Casein kinase 1, delta; CXCL6, C-X-C motif chemokine ligand 6; CXCR4, C-X-C motif Chemokine Receptor 4; DEFA4, Defensin Alpha 4; DEFB1, Defensin, beta-1; DHFR, Dihydrofolate Reductase; DKK3, Dickkopf 3; DUSP5, Dual specificity phosphatase 5; E4TF1-47 or GABPB1, GA binding protein transcription factor subunit beta-1; EDN1, Endothelin 1; EGF, Epidermal Growth Factor; EGR2, Early growth response 1; ELF3, E74-like factor 3 (ets domain transcription factor, epithelial specific); ELN, Elastin; EST22360, Expressed sequence tag 22360; EST22972, Expressed sequence tag 22972; EST43719, Expressed sequence tag 43719; FAP, Fibroblast Activation Protein Alpha; FAR2, Fatty Acyl-CoA Reductase 2; FFPE, Formalin Fixed Paraffin Embedded; FOXM1, Forkhead Box M1; FRAT1, Frequently rearranged in advanced T-cell lymphomas; G, Glomeruli; GN01 or STARD10, StAR-Related Lipid Transfer Domain-Containing 10; GP330, Glycoprotein 330; GPR183, G Protein-Coupled Receptor 183; GRM, Glutamate Metabotropic Receptor; HBEGF, Heparin-binding EGF-like growth factor; HD, High Density; HGF, Hepatocyte Growth Factor; HIF1A, Hypoxia-Inducible Factor 1 Subunit Alpha; HLA-E, Major Histocompatibility Complex, Class I, E; HPSE, Heparanase; HSPC121 or BIND1, Butyrate-induced transcript 1; IER3, Immediate early response 3; IFNG, Interferon Gamma; IFNGR1, Interferon gamma receptor 1; IGF1, Insulin-like growth factor 1; IL-6, Interleukin-6; ITGAX, Integrin Subunit Alpha X; ITGB2, Integrin Subunit Beta 2; ITGB5, Integrin Subunit Beta 5; JAK1, Janus kinase 1; KIF15, Kinesin Family Member 15; KCND3, Potassium voltage-gated channel, Shal-related subfamily, member 3; KRAS, KRAS Proto-Oncogene, GTPase; LAIR1, Leukocyte-Associated Immunoglobulin-Like Receptor 1; LAPTM5, Lysosomal Protein Transmembrane 5; LHFPL2, Lipoma HMGIC Fusion Partner-Like 2 Protein; LTB, Lymphotoxin beta; MAFF, V-MAF Musculoaponeurotic fibrosarcoma oncogene homolog F; MAN2B1, Mannosidase Alpha Class 2B Member 1; MAPK1, Mitogen-activated protein kinase 1; MARK3, MAP/microtubule affinity-regulating kinase 3; MBP45K, 45 kD protein megalin-binding protein; MCL1, Myeloid cell leukemia sequence 1 (BCL2-related); MCP-1, Monocyte Chemoattractant Protein-1; MERTK, MER Proto-Oncogene, Tyrosine Kinase; MET, Mesenchymal Epithelial Transition, Proto-Oncogene, Receptor Tyrosine Kinase; MPV17l, MPV17 Mitochondrial Inner Membrane Protein Like; MS4A6A, Membrane Spanning 4-Domains A6A; MUC18, Cell Surface Glycoprotein MUC18; MXI1, MAX Interactor 1, Dimerization Protein; NCF2, Neutrophil Cytosolic Factor 2; NDRG1, N-Myc Downstream-Regulated 1; NDST1, N-deacetylase/N-sulfotransferase 1; NMU, Neuromedin U; NNMT, Nicotinamide N-Methylransferase; OCT, Optical Coherence Tomography; OSF2, Osteoblast-specific factor 2; PAI-1, Plasminogen Activator Inhibitor 1 (or Serpine1—Serpin Family E Member 1); PDI, Protein disulfide isomerase; PFKFB3, 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3; PFKM, Phosphofructokinase, Muscle; PLD, Phospholipase D; PLEK P47, Pleckstrin P47; PPARγ, Peroxixome Proliferator-Activated Receptor gamma; PROLYL 2, Prolyl hydroxylase 2; pSTAT1, phospho-Signal Transducer and Activator of Transcription 1; PRC1, Protein Regulator of Cytokinesis 1; PRKD3, Protein kinase D3; PTDSS, Phosphatidylserine Synthase; PTPN1, Protein tyrosine phosphatase, non-receptor type 1; qRT-PCR, quantitative Real-Time Polimerase Chain Reaction; RAB4A, RAB4A, member RAS oncogene family; RBR107, Retinoblastoma-related protein; RORA, RAR-Related Orphan Receptor A; ROS1, V-ros UR2 sarcoma virus oncogene homolog 1; RRAS, Related RAS viral (r-ras) oncogene homolog; S100A6, S100 calcium-binding protein A6; SAMD4A, Sterile alpha motif domain-containing 4A; SEC6L1, SEC6-like 1; SEC14C1, SEC14-like 1; SERP1, Stress-associated endoplasmic reticulum protein 1; SLC13A3, Solute Carrier Family 13 member 3; SLC43A3, Solute Carrier Family 43 Member 3; SNX2, Sorting nexin 2; STAT, Signal Transducer and Activator of Transcription; STEAP1, Six transmembrane epithelial antigen of the prostate 1; TAX1BP1, Tax1 (human T-cell leukemia virus type I) binding protein 1; TCN1, Transcobalamin I (vitamin B12 binding protein, R binder family); TGF-β1, Transforming Growth Factor Beta-1; THBS3, Thrombospondin-3; TI, Tubule-Interstitium; TIA1, TIA1 cytotoxic granule-associated RNA-binding protein; TIMP1, Tissue Inhibitor of Metalloproteinase 1; TLR4, Toll Like Receptor 4; TMSB10, Thymosin β 10; TNFAIP6, TNF Alpha-Induced Protein 6; TOMM7, Translocase of outer mitochondrial membrane 7 homolog; TPST1, Tyrosylprotein sulfotransferase 1; TUBA1A, Tubulin α 1A; TYMS, Thymidylate synthetase; VEGFA, Vascular Endothelial Growth Factor A; VSIG4, V-Set and Immunoglobulin Domain-Containing 4; ZINC29IN4628, Human small zinc finger-like protein; ZNF33A, Zinc Finger Protein 33A