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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