Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades

Wang, Pei‐Wen; Wu, Tsung-Tien; Pan, Tai‐Long; Chen, Mu‐Hong; Goto, Shigeru; Chen, Chao‐Long

doi:10.3389/fimmu.2018.02216

Cited by 8 publications

(11 citation statements)

References 58 publications

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“…However, proteomic analysis has not been commonly used to study tolerance. The Chen group in Kaohsiung Chang Gung Memorial Hospital (Taiwan) has studied the proteomic signature of spontaneous tolerance in a rat model of LT (17,23,33). The rat models of tolerance can be induced spontaneously in LT between different strains (80).…”

Section: Discussionmentioning

confidence: 99%

“…Two-dimensional gel electrophoresis (2D gel)-based proteomics is the most widely used strategy described in selected publications (50%); however, shotgun proteomics has displaced this strategy, as this proteomic method has been applied most frequently in the last 5 years (62.5%). Only four of the publications used antibody arrays, two of which were in combination with 2D gel-based proteomics analyses (20,33) (Table 2). The application of prefractionation techniques to reduce the high dynamic range in protein abundance is increasing, as we observed that their use has doubled in the last 5 years (62.5% vs.21.4%).…”

Section: Proteomics Strategiesmentioning

confidence: 99%

“…In contrast, spontaneous tolerance in a rat model of LT was the main model used in the tolerance selected publications (17,23,33).…”

Section: Sample Sources and Study Typesmentioning

confidence: 99%

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Proteomics in Liver Transplantation: A Systematic Review

et al. 2021

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BackgroundAlthough proteomics has been employed in the study of several models of liver injury, proteomic methods have only recently been applied not only to biomarker discovery and validation but also to improve understanding of the molecular mechanisms involved in transplantation.MethodsThe study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and the guidelines for performing systematic literature reviews in bioinformatics (BiSLR). The PubMed, ScienceDirect, and Scopus databases were searched for publications through April 2020. Proteomics studies designed to understand liver transplant outcomes, including ischemia-reperfusion injury (IRI), rejection, or operational tolerance in human or rat samples that applied methodologies for differential expression analysis were considered.ResultsThe analysis included 22 studies after application of the inclusion and exclusion criteria. Among the 497 proteins annotated, 68 were shared between species and 10 were shared between sample sources. Among the types of studies analyzed, IRI and rejection shared a higher number of proteins. The most enriched pathway for liver biopsy samples, IRI, and rejection was metabolism, compared to cytokine-cytokine receptor interactions for tolerance.ConclusionsProteomics is a promising technique to detect large numbers of proteins. However, our study shows that several technical issues such as the identification of proteoforms or the dynamic range of protein concentration in clinical samples hinder the successful identification of biomarkers in liver transplantation. In addition, there is a need to minimize the experimental variability between studies, increase the sample size and remove high-abundance plasma proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Proteomics Strategiesmentioning

confidence: 99%

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Proteomics in Liver Transplantation: A Systematic Review

et al. 2021

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“…Researchers suggest that CER plays a role in tolerance in organ transplantation as a regulator of inflammation and oxidative injury. 18 Both A2MG and CER are important in the maintenance of metal ion levels 19 while AT3 is the major inhibitor of proteases. All together these proteins are crucial to sustain the pulmonary defence against inhaled pathogens.…”

Section: Discussionmentioning

confidence: 99%

<p>Plasma Acute Phase Proteins as Predictors of Chronic Lung Allograft Dysfunction in Lung Transplant Recipients</p>

Janciauskiene

Royer

Fuge

et al. 2020

JIR

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Cumulating reports suggest that acute phase proteins (APPs) have diagnostic and prognostic value in different clinical conditions. Among others, APPs are proposed to serve as markers that help to control the outcome of transplant recipients. Here, we questioned whether plasma concentrations of APPs mirror the development of chronic lung allograft dysfunction (CLAD). We performed blinded analysis of serial plasma samples retrospectively collected from 35 lung transplanted patients, of whom 25 developed CLAD and 10 remained stable during the follow-up period of 3 to 4.5 years. Albumin (ALB), alpha1-antitrypsin (AAT), high sensitivity C-reactive protein (CRPH), antithrombin-3 (AT3), ceruloplasmin (CER), and alpha2macroglobulin (A2MG) were measured by the nephelometric method. We found that within the first six months post-transplantation, levels of A2MG, CER and AAT were higher in stable patients relative to those who later developed CLAD. Moreover, in stable patient's plasma CRPH levels decreased during the follow-up period whereas opposite, in those developing CLAD, the CRPH gradually increased. The ALB levels became significantly lower at the end of the followup period in CLAD relative to a stable group. A logistic regression model based on A2MG, CER and AT3 at cutoffs levels of ≥175.5 mg/dL, ≥37.8 mg/dL and ≥27.35 mg/dL enabled to discriminate between stable and CLAD patients with a sensitivity of 87.5%, 100% and 62.5%, and specificity of 65.9%, 72.7% and 79.5%, respectively. We identified A2MG (below 175.5 mg/ dL) as an independent predictor of CLAD (hazard ratio 11.5, 95% CI (1.5-91.3), p<0.021). Our findings suggest that profiles of certain APPs may help to predict the development of lung dysfunction at the very early stages after transplantation.

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“…The 2-DE gels were then transferred to a PVDF membrane which was incubated overnight at 4 °C with the primary antibody for DNPH (Molecular Probes, Eugene, Oregon, USA) or fibrinogen (DAKO, Santa Clara, CA, USA). The blots were washed and incubated with goat anti-rabbit IgG conjugated HRP for 2 h. Enhanced chemiluminescence (Millipore, Burlington, MA, USA) was applied for detection [40].…”

Section: Methodsmentioning

confidence: 99%

Characterization of Fibrinogen as a Key Modulator in Patients with Wilson’s Diseases with Functional Proteomic Tools

Wang

Lin

Hung

et al. 2019

IJMS

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Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.

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Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades

Cited by 8 publications

References 58 publications

Proteomics in Liver Transplantation: A Systematic Review

Proteomics in Liver Transplantation: A Systematic Review

<p>Plasma Acute Phase Proteins as Predictors of Chronic Lung Allograft Dysfunction in Lung Transplant Recipients</p>

Characterization of Fibrinogen as a Key Modulator in Patients with Wilson’s Diseases with Functional Proteomic Tools

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