Indoxyl Sulfate-Mediated Metabolic Alteration of Transcriptome Signatures in Monocytes of Patients with End-Stage Renal Disease (ESRD)
Abstract
:1. Introduction
2. Results
2.1. Transcriptomic Analysis of Monocytes Derived from ESRD Patients and Monocytes Stimulated with Major Uremic Toxins, IS and PCS
2.2. Common Differentially Expressed Genes (DEGs) between ESRD Patient-Derived Monocytes and IS-Stimulated Monocytes
2.3. Principle Enriched Pathways in ESRD Patient-Derived Monocytes
2.4. Interaction Network Analysis of Common DEGs comparing ESRD Patient-Derived Monocytes and IS-Treated Monocytes
2.5. Experimental Validation of DEGs in IS-Treated Monocytes
3. Discussion
4. Materials and Methods
4.1. Peripheral Blood Mononuclear Cell (PBMC) Isolation
4.2. Sample Preparation for Microarray
4.3. Microarray Gene Expression Analysis
4.4. Data Preparation and Descriptive Statistics
4.5. Gene Expression Profiling and Analysis
4.6. Gene Set Enrichment Analysis
4.7. GO and Protein Pathway Analysis
4.8. Gene Functional Annotation and GO Annotation
4.9. Validation Microarray Genes-Quantitative RT-PCR
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Probe ID | Symbol | Gene Name | Fold Change (log2) | ||
---|---|---|---|---|---|
ESRD | IS | ||||
Top 50 Up-Regulated Genes | 16967771 | CXCL8 | C-X-C motif chemokine ligand 8 | 6.5945 | 0.3171 |
17000793 | CD14 | CD14 molecule | 6.1733 | 0.3099 | |
17058719 | NCF1C | neutrophil cytosolic factor 1C pseudogene | 4.9855 | 0.7591 | |
16716590 | MYOF | myoferlin | 4.7301 | 0.3701 | |
16857736 | MCEMP1 | mast cell expressed membrane protein 1 | 4.5776 | 0.6207 | |
16854486 | DSC2 | desmocollin 2 | 4.4608 | 0.3290 | |
16952874 | CCR1 | C-C motif chemokine receptor 1 | 4.3715 | 0.3022 | |
16869666 | ADGRE3 | adhesion G protein-coupled receptor E3 | 4.2049 | 0.7200 | |
16891082 | CYP27A1 | cytochrome P450 family 27 subfamily A member 1 | 4.0764 | 1.2708 | |
16709333 | TCF7L2 | transcription factor 7 like 2 | 3.9883 | 0.9611 | |
16684056 | FGR | FGR proto-oncogene, Src family tyrosine kinase | 3.8943 | 0.4057 | |
16768297 | DUSP6 | dual specificity phosphatase 6 | 3.8745 | 0.3807 | |
17086496 | DAPK1 | death associated protein kinase 1 | 3.8445 | 0.4779 | |
17059955 | PDK4 | pyruvate dehydrogenase kinase 4 | 3.5273 | 0.4756 | |
17096030 | FBP1 | fructose-bisphosphatase 1 | 3.4529 | 0.4545 | |
17046911 | NCF1B | neutrophil cytosolic factor 1B pseudogene | 3.3574 | 1.0349 | |
16896561 | CYP1B1 | cytochrome P450 family 1 subfamily B member 1 | 3.2051 | 1.5738 | |
16684144 | PTAFR | platelet activating factor receptor | 3.1942 | 0.3886 | |
17000724 | HBEGF | heparin binding EGF like growth factor | 2.8582 | 0.8480 | |
17044442 | SNX10 | sorting nexin 10 | 2.8334 | 0.3116 | |
16732985 | SLC37A2 | solute carrier family 37 member 2 | 2.7402 | 0.3424 | |
16658864 | PGD | phospho-gluconate dehydrogenase | 2.6875 | 0.7136 | |
17111711 | VSIG4 | V-set and immunoglobulin domain containing 4 | 2.6333 | 0.6154 | |
16805474 | ARRDC4 | arrestin domain containing 4 | 2.5744 | 0.3588 | |
16777685 | FLT3 | fms related tyrosine kinase 3 | 2.5176 | 0.4135 | |
17053697 | LOC644090 | uncharacterized LOC644090 | 2.4605 | 0.6179 | |
16991125 | NDST1 | N-deacetylase and N-sulfotransferase 1 | 2.3802 | 0.3088 | |
16669196 | CD101 | CD101 molecule | 2.2198 | 0.5474 | |
17063722 | CLEC5A | C-type lectin domain containing 5A | 2.2079 | 0.6715 | |
16875723 | TMEM150B | transmembrane protein 150B | 2.1721 | 0.3627 | |
16748788 | MGST1 | microsomal glutathione S-transferase 1 | 2.1668 | 0.8541 | |
16867784 | C3 | complement C3 | 2.1475 | 0.5078 | |
17121820 | USP32 | ubiquitin specific peptidase 32 | 2.1419 | 0.3092 | |
16929920 | H1F0 | H1 histone family member 0 | 2.0673 | 0.3007 | |
16848070 | SLC16A6 | solute carrier family 16 member 6 | 2.0182 | 0.4231 | |
16839524 | MIR22HG | MIR22 host gene | 2.0173 | 0.4588 | |
16774427 | LACC1 | laccase domain containing 1 | 1.9373 | 0.7574 | |
16729298 | ACER3 | alkaline ceramidase 3 | 1.9074 | 0.4178 | |
16894335 | ADAM17 | ADAM metallopeptidase domain 17 | 1.9073 | 0.3308 | |
17026267 | TNF | tumor necrosis factor | 1.8353 | 0.6968 | |
17013520 | SASH1 | SAM and SH3 domain containing 1 | 1.8301 | 0.6865 | |
17115636 | G6PD | glucose-6-phosphate dehydrogenase | 1.8165 | 0.4642 | |
16683445 | FUCA1 | alpha-L-fucosidase 1 | 1.7958 | 1.5007 | |
16876849 | ASAP2 | ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 | 1.7922 | 0.3036 | |
16852871 | SERPINB2 | serpin family B member 2 | 1.7359 | 2.2714 | |
17058978 | GSAP | gamma-secretase activating protein | 1.7231 | 0.3256 | |
17071162 | CPQ | carboxypeptidase Q | 1.7211 | 0.3579 | |
16968447 | GPAT3 | glycerol-3-phosphate acyltransferase 3 | 1.7197 | 0.3522 | |
16720318 | TALDO1 | trans-aldolase 1 | 1.6930 | 0.3785 | |
16688929 | GNG5 | G protein subunit gamma 5 | 1.6846 | 0.3409 | |
Top 50 Down-Regulated Genes | 16781893 | YME1L1 | YME1 like 1 ATPase | −5.1212 | −0.3594 |
16798132 | SNORD116-1 | small nucleolar RNA, C/D box 116-1 | −4.8499 | −0.8151 | |
17074313 | DEFA1B | defensin alpha 1B | −4.7542 | −0.3063 | |
16761201 | CD69 | CD69 molecule | −4.1940 | −0.3732 | |
16781830 | TRAJ17 | T cell receptor alpha joining 17 | −3.9577 | −0.3544 | |
16877297 | TRIB2 | tribbles pseudo-kinase 2 | −3.6828 | −0.3169 | |
16906571 | STAT4 | signal transducer and activator of transcription 4 | −3.6785 | −0.3412 | |
16798206 | SNORD116-20 | small nucleolar RNA, C/D box 116-20 | −3.3709 | −0.3708 | |
16672669 | LY9 | lymphocyte antigen 9 | −3.2701 | −0.3066 | |
16748205 | CLEC2D | C-type lectin domain family 2 member D | −3.2426 | −0.3819 | |
16761631 | DUSP16 | dual specificity phosphatase 16 | −3.1818 | −0.4038 | |
17110670 | PIM2 | Pim-2 proto-oncogene, serine/threonine kinase | −2.9802 | −0.6422 | |
16912130 | CST7 | cystatin F | −2.5494 | −0.3388 | |
17092767 | MLLT3 | MLLT3, super elongation complex subunit | −2.4775 | −0.7344 | |
16720085 | IFITM1 | interferon induced transmembrane protein 1 | −2.4475 | −0.3137 | |
17056849 | TRGV3 | T cell receptor gamma variable 3 | −2.4407 | −0.8184 | |
17005858 | HIST1H2AI | histone cluster 1 H2A family member i | −2.2799 | −0.4418 | |
16995717 | SNORD72 | small nucleolar RNA, C/D box 72 | −2.2604 | −0.7078 | |
17016503 | HIST1H3I | histone cluster 1 H3 family member i | −2.2455 | −0.4036 | |
16764564 | LIMA1 | LIM domain and actin binding 1 | −2.2305 | −0.3310 | |
16934045 | PIK3IP1 | phosphoinositide-3-kinase interacting protein 1 | −2.2022 | −0.4481 | |
16900737 | ANKRD36B | ankyrin repeat domain 36B | −2.0806 | −0.3064 | |
17016386 | HIST1H3D | histone cluster 1 H3 family member d | −2.0589 | −0.3624 | |
17122454 | ANKRD36 | ankyrin repeat domain 36 | −2.0333 | −0.5181 | |
17121094 | SRP54-AS1 | SRP54 antisense RNA 1 (head to head) | −1.9509 | −0.4420 | |
16756286 | C12orf75 | chromosome 12 open reading frame 75 | −1.8645 | −0.3758 | |
16798248 | SNHG14 | small nucleolar RNA host gene 14 | −1.8228 | −0.3124 | |
17122912 | ANKRD20A5P | ankyrin repeat domain 20 family member A5, pseudogene | −1.8010 | −0.3463 | |
16686060 | SLC2A1 | solute carrier family 2 member 1 | −1.7904 | −0.3997 | |
16968314 | PRDM8 | PR/SET domain 8 | −1.7855 | −0.5214 | |
17016383 | HIST1H4D | histone cluster 1 H4 family member d | −1.7560 | −0.3952 | |
16837296 | ARHGAP27P2 | Rho GTPase activating protein 27 pseudogene 2 | −1.7467 | −0.4159 | |
17005560 | HIST1H4C | histone cluster 1 H4 family member c | −1.7216 | −0.3526 | |
16849349 | TNRC6C-AS1 | TNRC6C antisense RNA 1 | −1.6941 | −0.6821 | |
17016360 | HIST1H4B | histone cluster 1 H4 family member b | −1.6893 | −0.5007 | |
17011708 | SLC16A10 | solute carrier family 16 member 10 | −1.6648 | −0.4770 | |
16780585 | GPR18 | G protein-coupled receptor 18 | −1.6552 | −0.4941 | |
17116745 | P2RY8 | P2Y receptor family member 8 | −1.6285 | −0.4951 | |
16987361 | ARSK | arylsulfatase family member K | −1.6196 | −0.3051 | |
16869324 | PRDX2 | peroxiredoxin 2 | −1.6134 | −0.4093 | |
16980528 | LRBA | LPS responsive beige-like anchor protein | −1.6071 | −0.3149 | |
16838300 | TMC8 | transmembrane channel like 8 | −1.5657 | −0.3583 | |
17100888 | LOC102723630 | uncharacterized LOC102723630 | −1.5554 | −0.4080 | |
16956983 | CBLB | Cbl proto-oncogene B | −1.5203 | −0.5545 | |
16930173 | APOBEC3D | apolipoprotein B mRNA editing enzyme catalytic subunit 3D | −1.5054 | −0.4054 | |
16985518 | PIK3R1 | phosphoinositide-3-kinase regulatory subunit 1 | −1.5016 | −0.5210 | |
17113606 | septin 6 | septin 6 | −1.5012 | −0.4799 | |
16993173 | LOC728554 | THO complex 3 pseudo-gene | −1.4969 | −0.3166 | |
16889160 | PLCL1 | phospholipase C like 1 (inactive) | −1.4891 | −0.3684 | |
17013197 | PEX3 | peroxisomal biogenesis factor 3 | −1.4474 | −0.3493 |
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Kim, H.Y.; Lee, S.J.; Hwang, Y.; Lee, G.H.; Yoon, C.E.; Kim, H.C.; Yoo, T.-H.; Lee, W.-W. Indoxyl Sulfate-Mediated Metabolic Alteration of Transcriptome Signatures in Monocytes of Patients with End-Stage Renal Disease (ESRD). Toxins 2020, 12, 621. https://doi.org/10.3390/toxins12100621
Kim HY, Lee SJ, Hwang Y, Lee GH, Yoon CE, Kim HC, Yoo T-H, Lee W-W. Indoxyl Sulfate-Mediated Metabolic Alteration of Transcriptome Signatures in Monocytes of Patients with End-Stage Renal Disease (ESRD). Toxins. 2020; 12(10):621. https://doi.org/10.3390/toxins12100621
Chicago/Turabian StyleKim, Hee Young, Su Jeong Lee, Yuri Hwang, Ga Hye Lee, Chae Eun Yoon, Hyeon Chang Kim, Tae-Hyun Yoo, and Won-Woo Lee. 2020. "Indoxyl Sulfate-Mediated Metabolic Alteration of Transcriptome Signatures in Monocytes of Patients with End-Stage Renal Disease (ESRD)" Toxins 12, no. 10: 621. https://doi.org/10.3390/toxins12100621