Susceptibility to COPD: Differential Proteomic Profiling after Acute Smoking

Franciosi, Lorenza; Postma, Dirkje S.; Berge, Maarten van den; Govorukhina, Natalia; Horvatovich, Péter; Fusetti, Fabrizia; Poolman, Berend; Lodewijk, Monique E.; Timens, Wim; Bischoff, Rainer; Hacken, Nicolaas ten

doi:10.1371/journal.pone.0102037

Cited by 31 publications

(31 citation statements)

References 47 publications

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“…Systemic Serpinb3a knockout mice are developmentally normal but display attenuated pro-inflammatory response in an asthma model [35]. This is in line with the elevated expression of SERPINB3/B4 in human airway inflammatory diseases [36-38]. Therefore, while the lack of overt developmental phenotype may be due to the compensatory effect of other Serpins such as Serpinb3b and Serpinb3c, it is also possible that SERPINB3/B4 mostly function as a stress-responsive factor.…”

Section: Mouse Homologues Of Serpinb3 and Serpinb4mentioning

confidence: 88%

“…Elevated expression of SERPINB3/B4 have been detected in chronic inflammatory conditions involving the skin, especially atopic dermatitis (AD)and psoriasis, as well as in respiratory inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis [36, 38, 41, 44-52]. …”

Section: Serpinb3/b4 In Inflammatory Diseasesmentioning

confidence: 99%

“…SERPINB3 protein is also elevated in epithelial lining fluid from the chronic obstructive pulmonary disease (COPD) patients after smoking [38, 42]. Similar as in the skin, Th2 cytokines IL-4 and IL-13 significantly induce SERPINB3/B4 expression in bronchial epithelial cells in a STAT6-dependent fashion [37, 42].…”

Section: Serpinb3/b4 In Inflammatory Diseasesmentioning

confidence: 99%

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SERPINB3 and B4: From biochemistry to biology

Sun

Sheshadri

Zong

2017

Seminars in Cell & Developmental Biology

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Human SERPINB3 and SERPINB4 are evolutionary duplicated serine/cysteine protease inhibitors. Genomic analysis indicates that these paralogous genes were encoded from independent loci arising from tandem gene duplication. Although the two molecules share 92% identity of their amino acid sequences, they are distinct in the Reactive Center Loop (RCL) including a hinge region and catalytic sequences which accounts for altered substrate specificity. Elevated expression of the two molecules have been reported to contribute to numerous pathological conditions such as inflammatory diseases and cancer. In this review, we focus on summarizing the biochemical features of SERPINB3/B4 and discussing the mechanistic basis for their biological functions and implications in human diseases.

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Section: Mouse Homologues Of Serpinb3 and Serpinb4mentioning

confidence: 88%

Section: Serpinb3/b4 In Inflammatory Diseasesmentioning

confidence: 99%

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SERPINB3 and B4: From biochemistry to biology

Sun

Sheshadri

Zong

2017

Seminars in Cell & Developmental Biology

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“…When compared to proteomic results from HBECs reported by Ali et al (2011), many proteins were overlapping such as calcium binding proteins of the S100-A family, proteases, and protein of the complement indicating an anti-inflammatory and anti-microbial role. Many of the proteins detected in MucilAir™ by our proteomics assay include markers such as aldehyde dehydrogenase (AL3A1), peroxiredoxin (PRDX), Serpins (SPBs), S100 proteins (S10A1, A2, A8), PIGR and others that are known to be up or down regulated in inflammation and COPD (Franciosi et al, 2014;Pelaia et al, 2014). Therefore, this proteomics panel could be used to map perturbations in the secreted protein profile following exposure to toxicants or complex mixtures such as cigarette smoke to evaluate adverse biological effects in vitro.…”

Section: Discussionmentioning

confidence: 99%

Targeted omics analyses, and metabolic enzyme activity assays demonstrate maintenance of key mucociliary characteristics in long term cultures of reconstituted human airway epithelia

Baxter

Thain²,

Banerjee

et al. 2015

Toxicology in Vitro

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3D reconstituted respiratory epithelia have emerged as better in vitro models for toxicological testing compared to cell lines due to the conservation of key morphological features and functions. MucilAir™ is a commercially available human airway epithelia system that can potentially maintain functional attributes for up to a year, however, detailed mucociliary characteristics and xenobiotic metabolism relevant to inhaled pro-toxicant bioactivation is lacking. Here, we assessed in MucilAir™ some key biomarkers that are characteristic of the respiratory epithelia including morphology, function and xenobiotics metabolism. The end points that were measured included targeted proteomics using a panel of 243 airway surface liquid (ASL) proteins, cilia beat frequency (CBF), a qRT-PCR screen of xenobiotic metabolizing enzymes, and CYP2A6/13, CYP1A1/1B1 activity. Comparison of ASL proteomics with human sputum identified key proteins common to both matrices, but present at different levels. Xenobiotic metabolism gene profiling demonstrated strong similarities with the normal human lung and did not reveal any consistent changes when assessed over a 6 month period. Inducibility and activity of CYP1A1/1B1 and activity of CYP2A6/2A13 were present at one month in culture and maintained in one tested MucilAir™ donor for several months. In conclusion, MucilAir™ presented important morphological and metabolic characteristics of a mucociliary epithelium in short and long term culture. MucilAir™ is therefore a potentially useful model to test repeated sub-cytotoxic doses of toxicants.

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“…The use of ELF in the COPD area was mainly promoted by Franciosi's team to investigate the proteomics of healthy subjects and COPD patients.…”

Section: Biological Fluidsmentioning

confidence: 99%

Searching for biomarkers of chronic obstructive pulmonary disease using proteomics: The current state

et al. 2018

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Detection of proteins which may be potential biomarkers of disorders represents a big step forward in understanding the molecular mechanisms that underlie pathological processes. In this context proteomics plays the important role of opening a path for the identification of molecular signatures that can potentially assist in early diagnosis of several clinical disturbances. Aim of this report is to provide an overview of the wide variety of proteomic strategies that have been applied to the investigation of chronic obstructive pulmonary disease (COPD), a severe disorder that causes an irreversible damage to the lungs and for which there is no cure yet. The results in this area published over the past decade show that proteomics indeed has the ability of monitoring alterations in expression profiles of proteins from fluids/tissues of patients affected by COPD and healthy controls. However, these data also suggest that proteomics, while being an attractive tool for the identification of novel pathological mediators of COPD, remains a technique mainly generated and developed in research laboratories. Great efforts dedicated to the validation of these biological signatures will result in the proof of their clinical utility.

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Susceptibility to COPD: Differential Proteomic Profiling after Acute Smoking

Cited by 31 publications

References 47 publications

SERPINB3 and B4: From biochemistry to biology

SERPINB3 and B4: From biochemistry to biology

Targeted omics analyses, and metabolic enzyme activity assays demonstrate maintenance of key mucociliary characteristics in long term cultures of reconstituted human airway epithelia

Searching for biomarkers of chronic obstructive pulmonary disease using proteomics: The current state

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