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Table 2 Some representative non-targeted proteomics studies in ARDS

From: Non-targeted proteomics of acute respiratory distress syndrome: clinical and research applications

Reference Samples Study objective Number of subjects Number of identified proteins; Top 5 up/down regulated proteins Proteomics methodology
[23] Bowler RP 2004 Plasma; Edema fluid in ARDS; BALF To expatiate the protein profiles 16 ARDS;
12 healthy
300 distinct protein spots;
158 proteins identified
↑: albumin, IgG, transferrin, clusterin and hemoglobin α2;
↓: Surfactant protein A, α1-antitrypsin, haptoglobin, GST and transthyretin
2D-PAGE; MALDI-TOF/MS
[24] De Torre C 2006 BALF To assess pulmonary inflammatory markers 11 ARDS;
33 healthy controls challenged with endotoxin
Only differentially expressed proteins reported ↑: Apo A1, S100A8, S100A9, AT III and transthyretin SELDI-TOF/MS;
2D-PAGE; MALDI-TOF/MS
[25] Schnapp LM 2006 BALF To collect a more complete protein profile 3 ARDS;
6 healthy
226, 291 and 659 proteins for the three patients studied ↑: albumin, ceruloplasmin, fibrinogen α chain, α1 chymotrypsin, α2-HS-glycoprotein and antitrypsin inhibitor 2D-HPLC;
Shotgun
Proteomics;
LC-MS/MS
[26] Gessner C 2008 Exhaled breath To find biomarkers of ARDS from EBC 24 ARDS;
10 healthy;
6 pneumonia (no ARDS)
3 proteins ↑: cytokeratins 2, 9, and 10 2D-PAGE; MALDI-TOF/MS
[27] Chang DW 2008 BALF To examine changes of protein expression by time ARDS on days 1 (n = 7), 3 (n = 8), and 7 (n = 5);
9 healthy
991 proteins spots seen. Only 80 proteins spots analyzed by MS which represented 37 unique proteins ↑: C3, S100A9, fibrinogen α chain, α1-antitrypsin, Apo A1 and hemopexin precursor 2D-PAGE; MALDI-TOF/MS
[28] Chen X 2013 Pooled plasma To expound novel biomarkers and identify the potential ARDS treatment targets 11 ARDS (Direct lung injury = 6, Indirect lung injury = 5);
15 healthy
132 proteins ↑: SAA, isoform 1 of CRP, α1-antichymotrypsin, Leucine-rich α2-glycoprotein and α1-AGP1
↓: complement factor H, Apo A1, serotransferrin, Apo C3 and Apo B100
MALDI TOF/TOF; iTRAQ;
LC-MS/MS
[29] Nguyen EV 2013 BALF To distinguish VAP in ARDS patients 30 ARDS: 14 VAP (+) and 16 VAP (−);
5 healthy
76 proteins ↑: in VAP (+): S100A8, elastase 2, lactotransferrin, actinin 1 and calnexin;
In VAP (−): β-hemoglobin, keratin 2, fibrinogen beta chain, SERPINF1 and fibronectin 1
2D-HPLC;
ESI-MS/MS
[30] Dong H 2013 Alveolar macrophage Comparative analysis of alveolar macrophage proteome in patients with ARDS 14 ARDS (severe infection):
6 Severe pancreatitis,
4 acute pyogenic cholangitis,
4 acute ileus
27 proteins ↑: (at the recovery phase): GSTP1, PEX13, S100A8/A9 and leukocyte elastase inhibitor;
(at the exudative phase): HSP27, annexin A8, cathepsin B, napsin A and galectin-3
2D-PAGE; MALDI-TOF/MS
[12] Bhargava M 2014 Pooled BALF To differentiate the proteomic profiles in that survivors from non-survivors 7 early phase ARDS survivors; 8 Early phase ARDS non-survivors;
7 late phase ARDS survivors
724 proteins identified; 499 proteins quantified ↑: (in early survivors): AT III, coagulation factor II/XII, plasminogen, complement C5/C1r, and hemopexin
(in early non-survivors): type I/III/V collagen and MMP 9
iTRAQ;
2D-HPLC; LC-MS/MS
[31] Liu D 2014 lung tissue To obtain global protein expression changes in ARDS lung tissues and find new therapeutic target of ARDS Pseudomonas aeruginosa-induced ALI rats 18 proteins ↑: peroxiredoxin 1, haptoglobin, GAPD, TCTP and VDBG;
↓: GSTA4, LGALS5, SPB1, transthyretin and Rho-associated protein kinase 1
MALDI-TOF/MS
[32] Tao J 2016 lung tissue To determine the mechanism underlying JGT treatment of ARDS 3 groups (Con, Mod, and JGT-H) 67 proteins ↑: Actn2, Ligp1, Serpina3n, Mcm2, and Myl4;
↓: Hbbt1, Hbbt2, Coq9, Agrn and S1pr1
LC/MS;
iTRAQ
LC Triple-TOF
[33] Xu X 2017 lung tissue To investigate the relationship between differentially expressed proteins (DEPs) and the pathogenesis of oleic acid (OA)-induced ALI in mice OA-treated ALI rat model and saline-treated mice 849 proteins were differentially expressed between the two groups, including 545 upregulated and 304 downregulated proteins ↑: C1qA, ASCC3, Piwi-like protein 2, hemoglobin β and Cxcl4;
↓: Collagen Alpha-1(V) Chain, GNAI1, chorion protein S18, VAMP3 and C-C motif chemokine 21a
iTRAQ
[34] Tao Z 2017 macrophage cells and lung tissue To explore the protective and therapeutic mechanisms of SFJDC in a rat model LPS-induced ALI rat models and saline-treated mice 4 proteins in lung tissues;23 overlapping candidate proteins in AMs ↑: TNFAIP8, β-hexosaminidase submit α, 5-oxoprolinase, apoptosis-inducing factor 1 and histone-arginine methyltransferase CARM1
↓: MAPRC1, DNAJB11, PRKCDBP, DNAJC5 and MAP6
HPLC-MS / MS,
[35] Ji Z 2017 serum of rat To find proteins may be detected in the plasma of patients at high risk of ARDS Rat model of ARDS was established by cecal ligation and puncture surgery 38 differentially expressed immunogenic proteins ↑: RASL11A, LOC689092, NUDT5, ENO1 and NEMF
↓: CHDH, Ankrd24, TEC, Phosphoglycerate kinase 1 and EPC1
2D-PAGE; MALDI-TOF/TOF
[14] Janga H 2018 H441 epithelial cells and endothelial cells To analyse the site-specific effects of LPS on the ACB and reveal the effects on the individual cell types and the ACB as a functional unit H441 epithelial cells and endothelial cells 5 proteins ↑: ICAM-1, VCAM-1, Angiopoietin 2, Macrophage colony-stimulating factor 1, complement C1r and cathepsin S LS-MS
[36] Yue X 2019 BALF To explore the pathogenic mechanisms of ARDS due to direct and indirect pulmonary insult control, intratracheal (I.T., direct) and intraperitoneal (I.P., indirect) LPS-treated mice 1017 proteins were identified;
The two LPS groups shared 13 up-regulated and 22 down-regulated proteins compared to the control group
↑: Apcs, H2afz, Hba-a1, Hist2h2aa2 and Hmgn2
↓: Anpep, Annexin A5, AU021092, Cadm1 and Cd200
Discovery-Based Quantitative Shotgun Proteomics
  1. BALF Bronchoalveolar lavage fluid, DIGE Difference in-gel electrophoresis, iTRAQ Isobaric tags for relative and absolute quantitation, MALDI-TOF/MS Matrix-assisted laser desorption/ionization-time of flight/mass spectrometry, SELDI Surface-enhanced laser desorption ionization, 2D-HPLC Two-dimensional high-performance liquid chromatography, 2D-PAGE Two-dimensional polyacrylamide gel electrophoresis, LC-MS Liquid chromatograph-mass spectrometer, ESI-MS Electrospray ionization-mass spectrometer, VAP Ventilator associated pneumonia, SFJDC ShuFengJieDu Capsule, ACB Alveolar-capillary barrier, up-regulated proteins, ↓ down-regulated proteins, GST Glutathione S-transferase, S100A8 calgranulin A, S100A9 calgranulin B, C3 Complement component C3, α1-AGP1 Alpha-1-acid glycoprotein 1, CRP C-reactive protein, SAA serum amyloid A protein, SERPINF1 serpin peptidase inhibitor, clade F, member 1, GSTP1 glutathione S-transferase pi-1. PEX13 Peroxisome biogenesis factor13, HSP27 Heat shock protein 27, MMP 9 matrix metallopeptidase 9, GAPD Glyceraldehyde-3-phosphate dehydrogenase, TCTP Translationally controlled tumor protein, VDBG Vitamin-D binding protein, GSTA4 Glutathione S-transferase alpha-4, LGALS5 Lectin, galactose binding, soluble 5, SBP1 Selenium-binding protein 1, C1qA Complement C1q subcomponent subunit A, ASCC3 Activating signal cointegrator 1 complex subunit 3, GNAI1 Guanine nucleotide-binding protein G(i) subunit alpha-1, VAMP3 Vesicle-associated membrane protein 3, TNFAIP8 tumor necrosis factor α-induced protein 8, MAPRC1 membrane-associated progesterone receptor component 1, DNAJB11 DnaJ homolog subfamily B member 11, PRKCDBP Protein kinase C delta-binding protein, DNAJC5 DnaJ homolog subfamily C member 5, MAP6 microtubule-associated protein 6, RASL11A RAS-like family 11 member A, LOC689092 Predicted: N-acetyllactosaminide β-1,6-N-acetylglucosaminyl-transferase, NUDT5 Predicted: ADP-sugar pyrophosphatase isoform X1, ENO1 Eno1 protein, NEMF Nuclear export mediator factor, CHDH Choline dehydrogenase, Ankrd24 Ankyrin repeat domain 24, TEC TEC protein tyrosine kinase, EPC1 Predicted: Enhancer of polycomb homolog 1 isoform X2, ICAM-1 intercellular cell adhesion molecule-1, VCAM-1 vascular cell adhesion molecule-1, Apcs Serum amyloid P-component, H2afz Histone H2A.Z, Hba-a1 Hemoglobin subunit alpha, Hist2h2aa2 Histone H2A type 2-A, Hmgn2 Non-histone chromosomal protein HMG-17, Anpep Aminopeptidase N, AU021092 UPF0764 protein C16orf89 homolog, Cadm1 Cell adhesion molecule 1, Cd200 OX-2 membrane glycoprotein