Table 2.
Transcriptomic patterns obtained by RNA-sequencing (RNA-seq) technique in isolated glomeruli and by Single Cell RNA-seq in whole renal tissue
| Authors | Year | Methodology | DEGs | Main findings |
|---|---|---|---|---|
| Isolated glomeruli | ||||
| Jiang et al. | 2016 | Illumina HiSeq 2000/2500 |
↑ JUN, FOS, PLAU (aging and inflammation); ↑ LL37 (senescent cells) |
Renal infiltration of aging neutrophils causes IgA-immune complex deposition, renal injury, activation of RAAS, complement, and coagulation cascade |
| Park et al. | 2020 | Illumina HiSeq 2500 |
↑ CCL3, CCL4, CXCL16 (Inflammation); ↑ BTK, SYK, MAPK1 (B cell and Fcγ-R pathways); ↑ TNF, TGFBR1, SMAD3, SMAD5, COL1A1 (fibrosis); ↑ GRK2, HIF1A, PI3KCA (PI3K-Akt pathways); ↑ C4A, C4B (complement); ↑ B4GALT1 (mesangial receptor for IgA); ↓ DUSP1, MALAT1, CARMN, FOS ↓ FOSB, JUN (FOS-JUN pathway); ↓AGTR1, RGS2, RGS16, RGS11 (regulators of the inflammation) |
SYK is increased in mesangial cells by signals initiated by IgA1. Thus, this molecule may be considered a potential target for specific drugs |
| Whole renal tissue | ||||
| Zheng et al. | 2020 | STRT scRNA-seq |
Renal cortex—Resident cells ↑ ATN1, PDGFRB, COL1A2; LUM (mesangial cells); ↑ PCOLCE2, NPHS2, WT1 (podocytes); ↑ AQP2, AQP3 (tubular cells); ↑ AQP6 (intercalated cells); ↑ SLC5A12, CUBN (proximal tubules); ↑ SLC12A1 (loop cells of Henle); ↑ JCHAIN (mesangial cells) Renal cortex—Non-resident cells ↑ CD3D, CD3E (T-cells); ↑ CD14, CD68, ITGAM (macrophages) Inflammation process ↑ THY1 (mesangial proliferation); ↑ Genes encoding collagen 5, glycoproteins, integrins; ↑ FN1 (ECM component that aids IgAN deposition); ↑ WFDC2 (protease inhibitor); ↑ SPP1, KNG1 (inflammatory mediators); ↑ PLGRKT, CCL2 (cytokines); ↑ AOC3 (leukocyte trafficking) Chronic inflammation ↑ PLGRKT2; ↑ CCL2, CX3CR1 (Macrophage activation); ↑ IFI44, IFI44L, IFI6, ISG15 (interferon response); ↑ FCGR3A, GZMB, KLRD, FGFBP2, GZMH (CD8+ T-cell cytotoxicity) Intercalated cells and fibrosis ↑ S100A4, ZEB1, ZEB2 |
ANGPT1/TEK interaction is the most prominent mesangial-endothelial cell–cell interaction |
| Tang et al. | 2021 | Illumina HiSeq X10 |
Glomerular cells ↑MALAT1, GADD45B, SOX4, EDIL3, FOS (mesangial cells); ↑ SOX4, MT-RNR1, PECAM1, UTRN, MT-ATP6P1, MT- ND4L (endothelial cells); ↑ PRSS23, NGF, HES1, (podocytes); ↑ SELP, PECAM1 (cell adhesion); ↑ SOX4, ACKR1, RNASE1 (endothelial cells) Tubular cells ↑ TNF, IL-17, NOD (epithelial cells); ↑ p38MAPK (distal tubule); ↑ ITGB6, ITGB8, YWHAH, SPP1, JUN, FOS (Henle cells); ↑ NFKBIA, TXNIP, CXCL3, CXCL2 (principal and intercalated cells) Non-resident cells ↓ GPX3, FAM49B, FCGBP (renal macrophages); Cell–cell crosstalk ↑ CXCL1, CCL2 (mesangial cells); ↑ ACKR1 (endothelial junctions); ↑ JAGGED1, NOTCH4 (endothelial cells); ↑ FGF2, PDGFD (proliferation and matrix production in mesangial cells) Overt proteinuria ↑ SPARC, ROCK2 (mesangial cells); ↑ TXNIP, SPARCL1, CD74 (endothelial cells) |
The molecular inflammatory process moves from the mesangial cells to other cells combined with non-resident circulating cells. Proteinuria induces overexpression of genes at glomerular and tubular level leading to renal fibrosis |
| Chen et al. | 2021 | 10X Genomix scRNA-seq |
↑ MMP7, MYC (wnt-β catenin target genes activated in proximal tubular cells); ↑ FXYD5, CD74, B2M (podocytes); ↑ CLIC1, RPS26, LTB (mesangial cells) |
Jun B gene may be a novel prognostic biomarker in IgAN |
ACKR1, Atypical Chemokine Receptor 1; AGTR1, Angiotensin II Receptor Type 1; ANGPT1, Angiopoietin 1; AOC3, Amine Oxidase Copper-Containing 3; ATN1, Atrophin 1; AQP2, Aquaporin 2; AQP3, Aquaporin 3; AQP6, Aquaporin 6; B2M, Beta-2-Microglobulin; B4GALT1, Beta-1,4-Galactosyltransferase 1; BTK, Bruton Tyrosine Kinase; C4A, Complement C4A; C4B, Complement C4B; CARMN, Cardiac Mesoderm Enhancer-Associated Non-Coding RNA; CCL2, C–C Motif Chemokine Ligand 2; CCL3, C–C motif chemokine ligand 3; CCL4, C–C motif chemokine ligand 4; CD3D, T-Cell Surface Glycoprotein CD3 Delta Chain; CD3E, T-Cell Surface Glycoprotein CD3 Epsilon Chain; CD14, Monocyte Differentiation Antigen CD14; CD68, Macrophage Antigen CD68; CD74, CD74 Molecule; CLIC1, Chloride Intracellular Channel 1; COL1A1, Collagen Type I Alpha 1 Chain; COL1A2, Collagen Type I Alpha 2 Chain; CUBN, Cubilin; CX3CR1, C-X3-C Motif Chemokine Receptor 1; CXCL1, C-X-C Motif Chemokine Ligand 1; CXCL2, C-X-C Motif Chemokine Ligand 2; CXCL3, C-X-C Motif Chemokine Ligand 3; CXCL16, C-X-C motif chemokine ligand 16; DUSP1, Dual Specificity Phosphatase 1; ECM, Extra-cellular matrix; EDIL3, EGF-Like Repeats and Discoidin Domains 3; FAM49B, Family with Sequence Similarity 49, Member B; FCGBP, Fc Fragment Of IgG-Binding Protein; FCGR3A, Fc Fragment of IgG Receptor IIIa; FGF2, Fibroblast Growth Factor 2; FGFBP2, Fibroblast Growth Factor-Binding Protein 2; FN1, Fibronectin 1; FOS, Fos Proto-Oncogene, AP-1 Transcription Factor Subunit; FOSB, FosB Proto-Oncogene, AP-1 Transcription Factor Subunit; FXYD5, FXYD Domain-Containing Ion Transport Regulator 5; GADD45B, Growth Arrest and DNA Damage-Inducible Beta; GPX3, Glutathione Peroxidase 3; GRK2, G Protein-Coupled Receptor Kinase 2; GZMB, Granzyme B; GZMH, Granzyme H; HES1, Hes Family BHLH Transcription Factor 1; HIF1A, Hypoxia-Inducible Factor 1 Subunit Alpha; IFI6, Interferon Alpha-Inducible Protein 6; IFI44, Interferon-Induced Protein 44; IFI44L, Interferon-Induced Protein 44 Like; IgAN, Immunoglobulin A nephropathy; IL-17, Interleukin-17; ISG15, ISG15 Ubiquitin-Like Modifier; ITGAM, Integrin Subunit Alpha M; ITGB6, Integrin Subunit Beta 6; ITGB8, Integrin Subunit Beta 8; JAGGED1, Jagged Canonical Notch Ligand 1; JCHAIN, Joining Chain of Multimeric IgA and IgM; JUN, Jun Proto-Oncogene, AP-1 Transcription Factor Subunit; KLRD, Killer Cell Lectin-Like Receptor D; KNG1, Kininogen 1; LL37 or CAMP, Cathelicidin Antimicrobial Peptide; LTB, Lymphotoxin Beta; LUM, Lumican; MALAT1, Metastasis-Associated Lung Adenocarcinoma Transcript 1; MAPK1, Mitogen-Activated Protein Kinase 1; MMP7, Matrix Metallopeptidase 7; MT-ATP6P1, MT-ATP6 Pseudogene 1; MT-ND4L, Mitochondrially Encoded NADH:Ubiquinone Oxidoreductase Core Subunit 4L; MT-RNR1, Mitochondrially Encoded 12S RRNA; MYC, MYC Proto-Oncogene, BHLH Transcription Factor; NFKBIA, NFKB Inhibitor Alpha; NGF, Nerve Growth Factor; NOD, Nucleotide-Binding Oligomerization Domain Containing; NOTCH4, Notch Receptor 4; NPHS2, NPHS2 Stomatin Family Member, Podocin; p38MAPK, p38 Mitogen-Activated Protein Kinase; PCOLCE2, Procollagen C-Endopeptidase Enhancer 2; PDGFRB, Platelet-Derived Growth Factor Receptor Beta; PDGFD, Platelet-Derived Growth Factor D; PECAM1, Platelet and Endothelial Cell Adhesion Molecule 1; PI3KCA, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha; PLAU, Plasminogen Activator, Urokinase; PLGRKT, Plasminogen Receptor with A C-Terminal Lysine; PLGRKT2, Plasminogen Receptor with A C-Terminal Lysine 2; PRSS23, Serine Protease 23; RGS2, Regulator of G Protein-Signaling 2; RGS11, Regulator of G Protein-Signaling 11; RGS16, Regulator of G Protein-Signaling 16; RNASE1, Ribonuclease A Family Member 1; ROCK2, Rho-Associated Coiled-Coil Containing Protein Kinase 2; RPS26, Ribosomal Protein S26; S100A4, S100 Calcium-Binding Protein A4; SELP, Selectin P; SLC12A1, Solute Carrier Family 12 Member 1; SLC5A12, Solute Carrier Family 5 Member 12; SMAD3, SMAD Family Member 3; SMAD5, SMAD Family Member 5; SOX4, SRY-Box Transcription Factor 4; SPARC, Secreted Protein Acidic and Cysteine Rich; SPARCL1, SPARC Like 1; SPP1, Secreted Phosphoprotein 1; SYK, Spleen-Associated Tyrosine Kinase; TEK, TEK Receptor Tyrosine Kinase; THY, Thy-1 T-Cell Surface Antigen; TNF, Tumor Necrosis Factor; TGFBR1, Transforming Growth Factor Beta Receptor 1; TXNIP, Thioredoxin-Interacting Protein; UTRN, Utrophin; WFDC2, WAP Four-Disulfide Core Domain 2; WNT, Wingless-Type MMTV Integration Site Family; WT1, Wilms Tumor 1 Transcription Factor; YWHAH, Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Eta; ZEB1, Zinc Finger E-Box-Binding Homeobox 1; ZEB2, Zinc Finger E-Box-Binding Homeobox 2