scholarly journals “Degradation of the extracellular matrix is part of the pathology of ulcerative colitis”

2018 ◽  
Author(s):  
Stefan Kirov ◽  
Ariella Sasson ◽  
Clarence Zhang ◽  
Scott Chasalow ◽  
Ashok Dongre ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Extracellular Matrix ◽  
Proteomics Data ◽  
Post Translational Modifications ◽  
Mrna Expression Data ◽  
Colon Biopsy ◽  
Protein Expressions ◽  
Ecm Degradation ◽  
Scientific Value ◽  
Compensatory Regulation

AbstractThe scientific value of re-analyzing existing datasets is often proportional to the complexity of the data. Proteomics data are inherently complex and can be analyzed at many levels, including proteins, peptides, and post-translational modifications to verify and/or develop new hypotheses. In this paper, we present our re-analysis of a previously published study comparing colon biopsy samples from ulcerative colitis (UC) patients to non-affected controls. In addition to confirming and reinforcing the original finding of upregulation of neutrophil extracellular traps (NETs), we report novel findings, including that Extracellular Matrix (ECM) degradation and neutrophil maturation are involved in the pathology of UC. The pharmaceutically most relevant differential protein expressions were confirmed using immunohistochemistry as an orthogonal method. As part of this study, we also compared proteomics data to previously published mRNA expression data. These comparisons indicated compensatory regulation at transcription levels of the ECM proteins we identified and open possible new venues for drug discovery.

scholarly journals The olfactory secretome varies according to season in female sheep and goat

2019 ◽  
Author(s):  
Paul CANN ◽  
Malika CHABI ◽  
Aliénor DELSART ◽  
Chrystelle LE DANVIC ◽  
Jean-Michel SALIOU ◽  
...  
Keyword(s):  
Sexual Activity ◽  
Hormonal Control ◽  
Physiological Status ◽  
Sexually Active ◽  
Hormonal Changes ◽  
Seasonal Breeding ◽  
Proteomics Data ◽  
Specific Expression ◽  
Two Dimensional Gel Electrophoresis ◽  
Post Translational Modifications

Abstract Abstract: Background : Small ungulates (sheep and goat) display a seasonal breeding, characterised by two successive periods, sexual activity (SA) and sexual rest (SR). Odours emitted by a sexually active male can reactivate the ovulation of anoestrus females. The plasticity of the olfactory system under these hormonal changes has never been explored at the peripheral level of odours reception. As it was shown in pig that the olfactory secretome (proteins secreted in the nasal mucus) could be modified under hormonal control, we monitored its composition in females of both species through several reproductive seasons, thanks to a non-invasive sampling of olfactory mucus. For this purpose, two-dimensional gel electrophoresis (2D-E), western-blot with specific antibodies, MALDI-TOF and high-resolution (nano-LC-MS/MS) mass spectrometry, RACE-PCR and molecular modelling were used. Results : In both species the olfactory secretome is composed of isoforms of OBP-like proteins, generated by post-translational modifications, as phosphorylation, N-glycosylation and O -GlcNAcylation. Important changes were observed in the olfactory secretome between the sexual rest and the sexual activity periods, characterised in ewe by the specific expression of SAL-like proteins and the emergence of OBPs O- GlcNAcylation. In goat, the differences between SA and SR did not come from new proteins expression, but from different post-translational modifications, the main difference between the SA and SR secretome being the number of isoforms of each protein. Proteomics data are available via ProteomeXchange with identifier PXD014833. Conclusion : Despite common behaviour, seasonal breeding, and genetic resources, the two species seem to adapt their sensory equipment in SA by different modalities: the variation of olfactory secretome in ewe could correspond to a specialization to detect male odours only in SA, whereas in goat the stability of the olfactory secretome could indicate a constant capacity of odours detection suggesting that the hallmark of SA in goat might be the emission of specific odours by the sexually active male. In both species, the olfactory secretome is a phenotype reflecting the physiological status of females, and could be used by breeders to monitor their receptivity to the male effect.

scholarly journals The Arabidopsis thaliana PeptideAtlas; harnessing world-wide proteomics data for a comprehensive community proteomics resource

2021 ◽  
Author(s):  
Klaas Jan van Wijk ◽  
Eric W Deutsch ◽  
Qi Sun ◽  
Zhi Sun ◽  
Tami Leppert ◽  
...  
Keyword(s):  
Splice Variants ◽  
Community Resources ◽  
Proteomics Data ◽  
Post Translational Modifications ◽  
Arabidopsis Proteome ◽  
Metadata Annotation ◽  
Protein Properties ◽  
Specific Proteins ◽  
Protein Splice ◽  
Splice Forms

We developed a new resource, the Arabidopsis PeptideAtlas (www.peptideatlas.org/builds/arabidopsis/), to solve central questions about the Arabidopsis proteome, such as the significance of protein splice forms, post-translational modifications (PTMs), or simply obtain reliable information about specific proteins. PeptideAtlas is based on published mass spectrometry (MS) analyses collected through ProteomeXchange and reanalyzed through a uniform processing and metadata annotation pipeline. All matched MS-derived peptide data are linked to spectral, technical and biological metadata. Nearly 40 million out of ~143 million MSMS spectra were matched to the reference genome Araport11, identifying ~0.5 million unique peptides and 17858 uniquely identified proteins (only isoform per gene) at the highest confidence level (FDR 0.0004; 2 non-nested peptides ≥ 9 aa each), assigned canonical proteins, and 3543 lower confidence proteins. Physicochemical protein properties were evaluated for targeted identification of unobserved proteins. Additional proteins and isoforms currently not in Araport11 were identified, generated from pseudogenes, alternative start, stops and/or splice variants and sORFs; these features should be considered for updates to the Arabidopsis genome. Phosphorylation can be inspected through a sophisticated PTM viewer. This new PeptideAtlas is integrated with community resources including TAIR, tracks in JBrowse, PPDB and UniProtKB. Subsequent PeptideAtlas builds will incorporate millions more MS data.

scholarly journals STIM1- and Orai1-mediated Ca2+ oscillation orchestrates invadopodium formation and melanoma invasion

2014 ◽  
Vol 207 (4) ◽  
pp. 535-548 ◽  
Author(s):  
Jianwei Sun ◽  
Fujian Lu ◽  
Huifang He ◽  
Junling Shen ◽  
Jane Messina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Melanoma Invasion ◽  
Ecm Degradation ◽  
Underlying Mechanisms

Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, and yet, the underlying mechanisms remained largely unknown. In this paper, we report that STIM1- and Orai1-mediated Ca2+ oscillations promote melanoma invasion by orchestrating invadopodium assembly and extracellular matrix (ECM) degradation. Ca2+ oscillation signals facilitate invadopodial precursor assembly by activating Src. Disruption of Ca2+ oscillations inhibited invadopodium assembly. Furthermore, STIM1 and Orai1 regulate the proteolysis activity of individual invadopodia. Mechanistically, Orai1 blockade inhibited the recycling of MT1–matrix metalloproteinase (MMP) to the plasma membrane and entrapped MT1-MMP in the endocytic compartment to inhibit ECM degradation. STIM1 knockdown significantly inhibited melanoma lung metastasis in a xenograft mouse model, implicating the importance of this pathway in metastatic dissemination. Our findings provide a novel mechanism for Ca2+-mediated cancer cell invasion and shed new light on the spatiotemporal organization of store-operated Ca2+ signals during melanoma invasion and metastasis.

LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis

Cartilage ◽  
2019 ◽  
pp. 194760351985575 ◽  
Author(s):  
Kang Chen ◽  
Hao Zhu ◽  
Min-Qian Zheng ◽  
Qi-Rong Dong
Keyword(s):  
Extracellular Matrix ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Regulatory Function ◽  
Qrt Pcr ◽  
Ecm Degradation ◽  
Competitive Endogenous Rna

Background As a degenerative joint disease, osteoarthritis (OA) is characterized by articular cartilage degradation. Long noncoding RNAs (lncRNAs) act critical roles in the regulation of OA development, including affecting the proliferation, apoptosis, extracellular matrix (ECM) degradation, and inflammatory response of chondrocytes. The current study’s aim was to investigate the regulatory function and the underlying molecular mechanism of lncRNA MEG3 in ECM degradation of chondrocytes in OA. Methods In the current study, chondrocytes were induced by interleukin-1β (IL-1β) to simulate OA condition, and further assessed cell viability, lncRNA MEG3 and miR-93 expression levels. Overexpression or knockdown of lncRNA MEG3 in chondrocytes treated with IL-1β were performed to investigate the function of MEG3 in regulating cell proliferation, apoptosis and ECM degradation using EdU assay, flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. The interaction between MEG3 and miR-93 was assessed using qRT-PCR. Furthermore, overexpression of miR-93 was performed as recovery experiment to explore the functional mechanism of MEG3. Results MEG3 was significantly downregulated in chondrocytes treated with IL-1β, whereas miR-93 was upregulated concomitantly. Overexpression of MEG3 induced the proliferation, suppressed the apoptosis, and relieved the degradation of ECM in IL-1β-induced chondrocytes. By contrast, knockdown of MEG3 suppressed the proliferation, promoted the apoptosis, and aggravated ECM degradation in IL-1β induced chondrocytes. In addition, MEG3 was found to relieve the inhibitive expression of TGFBR2 as a competitive endogenous RNA (ceRNA) of miR-93, and then activated transforming growth factor-β (TGF-β) signaling pathway, regulated chondrocytes ECM degradation in IL-1β induced chondrocytes subsequently. Conclusion LncRNA MEG3 targeted miR-93/TGFBR2 axis, regulated the proliferation, apoptosis and ECM degradation of chondrocytes in OA.

scholarly journals Spatiotemporal Coupling of Focal Extracellular Matrix Degradation and Reconstruction in the Menstrual Human Endometrium

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5094-5105 ◽  
Author(s):  
Héloïse P. Gaide Chevronnay ◽  
Christine Galant ◽  
Pascale Lemoine ◽  
Pierre J. Courtoy ◽  
Etienne Marbaix ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Expression Profiles ◽  
Xenograft Model ◽  
Gene Expression Profiles ◽  
Functional Layer ◽  
Processing Enzymes ◽  
Mouse Xenograft Model ◽  
Glandular Cells ◽  
Tissue Degradation ◽  
Ecm Degradation

Coupling of focal degradation and renewal of the functional layer of menstrual endometrium is a key event of the female reproductive biology. The precise mechanisms by which the various endometrial cell populations control extracellular matrix (ECM) degradation in the functionalis while preserving the basalis and the respective contribution of basalis and functionalis in endometrium regeneration are still unclear. We therefore compared the transcriptome of stromal and glandular cells isolated by laser capture microdissection from the basalis as well as degraded and preserved areas of the functionalis in menstrual endometria. Data were validated by in situ hybridization. Expression profile of selected genes was further analyzed throughout the menstrual cycle, and their response to ovarian steroids withdrawal was studied in a mouse xenograft model. Immunohistochemistry confirmed the results at the protein level. Algorithms for sample clustering segregated biological samples according to cell type and tissue depth, indicating distinct gene expression profiles. Pairwise comparisons identified the greatest numbers of differentially expressed genes in the lysed functionalis when compared with the basalis. Strikingly, in addition to genes products associated with tissue degradation (matrix metalloproteinase and plasmin systems) and apoptosis, superficial lysed stroma was enriched in gene products associated with ECM biosynthesis (collagens and their processing enzymes). These results support the hypothesis that fragments of the functionalis participate in endometrial regeneration during late menstruation. Moreover, menstrual reflux of lysed fragments overexpressing ECM components and adhesion molecules could easily facilitate implantation of endometriotic lesions.

scholarly journals Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 619 ◽  
Author(s):  
Arthur T. Kopylov ◽  
Alexander A. Stepanov ◽  
Kristina A. Malsagova ◽  
Deepesh Soni ◽  
Nikolay E. Kushlinsky ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Matrix ◽  
Tumor Growth ◽  
Binding Protein ◽  
Lectin Pathway ◽  
Protein Markers ◽  
Aseptic Inflammation ◽  
Post Translational Modifications ◽  
Early Stages ◽  
Native Proteins

Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.

Post-translational modifications of the extracellular matrix are key events in cancer progression: Opportunities for biochemical marker development

Biomarkers ◽  
2011 ◽  
Vol 16 (3) ◽  
pp. 193-205 ◽  
Author(s):  
D. J. Leeming ◽  
A. C. Bay-Jensen ◽  
E. Vassiliadis ◽  
M. R. Larsen ◽  
K. Henriksen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Biochemical Marker ◽  
Marker Development ◽  
Post Translational Modifications ◽  
Key Events

scholarly journals Identification of a novel ADAMTS9/GON-1 function for protein transport from the ER to the Golgi

2012 ◽  
Vol 23 (9) ◽  
pp. 1728-1741 ◽  
Author(s):  
Sawako Yoshina ◽  
Kenjiro Sakaki ◽  
Aki Yonezumi-Hayashi ◽  
Keiko Gengyo-Ando ◽  
Hideshi Inoue ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endoplasmic Reticulum ◽  
Protease Activity ◽  
Protein Transport ◽  
Type I ◽  
C Elegans ◽  
Domain Structures ◽  
Ecm Proteins ◽  
Ecm Degradation ◽  
Similar Domain

A disintegrin-like and metalloprotease with thrombospondin type I motif (ADAMTS9) is a member of the secreted metalloprotease family that is believed to digest extracellular matrix (ECM) proteins outside of cells. Its Caenorhabditis elegans orthologue, GON-1, is involved in ECM degradation and is required for gonad morphogenesis. ADAMTS9 and GON-1 have similar domain structures, and both have a unique C-terminal domain called the “GON domain,” whose function remains unknown. Here we show that down-regulation of human ADAMTS9 and C. elegans GON-1 results in the inhibition of protein transport from the endoplasmic reticulum (ER) to the Golgi. This phenotype was rescued by the expression of the GON domain localizing in the ER in human cells and C. elegans. We propose a novel function of ADAMTS9 and GON-1 in the ER that promotes protein transport from the ER to the Golgi. This function is GON-domain dependent but protease activity independent.

scholarly journals Parasites, proteomes and systems: has Descartes’ clock run out of time?

Parasitology ◽  
2012 ◽  
Vol 139 (9) ◽  
pp. 1103-1118 ◽  
Author(s):  
J. M. WASTLING ◽  
S. D. ARMSTRONG ◽  
R. KRISHNA ◽  
D. XIA
Keyword(s):  
Systems Biology ◽  
Protein Interactions ◽  
Biological Data ◽  
Protein Protein Interactions ◽  
Proteomics Data ◽  
Data Types ◽  
Quality Of Data ◽  
Post Translational Modifications ◽  
Systems Modelling ◽  
New Generation

SUMMARYSystems biology aims to integrate multiple biological data types such as genomics, transcriptomics and proteomics across different levels of structure and scale; it represents an emerging paradigm in the scientific process which challenges the reductionism that has dominated biomedical research for hundreds of years. Systems biology will nevertheless only be successful if the technologies on which it is based are able to deliver the required type and quality of data. In this review we discuss how well positioned is proteomics to deliver the data necessary to support meaningful systems modelling in parasite biology. We summarise the current state of identification proteomics in parasites, but argue that a new generation of quantitative proteomics data is now needed to underpin effective systems modelling. We discuss the challenges faced to acquire more complete knowledge of protein post-translational modifications, protein turnover and protein-protein interactions in parasites. Finally we highlight the central role of proteome-informatics in ensuring that proteomics data is readily accessible to the user-community and can be translated and integrated with other relevant data types.

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