Quantitative mass spectrometry of diabetic kidney tubules identifies GRAP as a novel regulator of TGF-β signaling

Cummins, Timothy D.; Barati, Michelle T.; Coventry, Susan; Salyer, Sarah A.; Klein, Jon B.; Powell, David W.

doi:10.1016/j.bbapap.2009.09.029

Cited by 29 publications

(35 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, our gene expression analysis showed an upregulation of the GRAP gene, encoding the GRB2-related adaptor protein, responsible for the coupling of signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. On this basis, it is tempting to speculate that this adaptor has a role in DFSP progression (39).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Stacchiotti¹,

Pantaleo²,

Negri³

et al. 2015

Clin Cancer Res

View full text Add to dashboard Cite

Purpose: To report on imatinib mesylate (IM) in patients with metastatic dermatofibrosarcoma protuberans (DFSP)/fibrosarcomatous (FS)-DFSP and on the impact of the treatment on tumor biology.Experimental design: Ten consecutive patients treated with IM from 2007 to 2015 for a metastatic relapse from DFSP/FS-DFSP were identified. FISH analysis for COL1A1-PDGFB was performed. Two IM-treated and 4 na€ ve FS-DFSP were transcriptionally profiled by RNAseq on HiScanSQ platform. Differential gene expression was analyzed with edgeR (Bioconductor), followed by hierarchical clustering and Principal Component Analysis.Results: All cases featured fibrosarcomatous in the metastasis and retained the COL1A1-PDGFB. Best RECIST response was: 8 partial response, 1 stable disease, and 1 progressive disease. Median progression-free survival was 11 months. Five patients received surgery after IM and all relapsed. IM was restored in 4 patients with a new response. After IM, the most upregulated genes included those encoding for immunoglobulins and those affecting functions and differentiation of endothelial cells. Pathway enrichment analysis revealed upregulation in genes involved in antigen processing and presentation, natural killer-mediated cytotoxicity, and drug and xenobiotics metabolism. Conversely, a significant down-regulation of kinase signaling pathways was detected.Conclusions: All metastatic cases were fibrosarcomatous. Most patients responded to IM, but PFS was shorter than reported in published series which included both DFSP and FS-DFSP. All patients operated after IM had a relapse, suggesting that IM cannot eradicate metastatic cases and that the role of surgery is limited. Transcriptional profile of na€ ve and posttreatment samples pointed the contribution of immune infiltrates in sustaining the response to IM.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Stacchiotti¹,

Pantaleo²,

Negri³

et al. 2015

Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…33,35 The amount of antibacterial proteins was almost doubled in b-MVs, whereas no difference was observed in the amount of cytoskeletal or metabolic proteins ( Figure 4B). Analyzing at the level of individual proteins, 29 proteins were identified from the 100 most highly expressed proteins that were increased by at least 40% in b-MVs, including 11 of the 20 most highly expressed proteins (supplemental Table 2).…”

Section: Neutrophil-derived Antibacterial Microvesicles 513mentioning

confidence: 98%

“…32 MVs extracts were analyzed with a Thermo LTQ linear ion trap using a previously described 2D-LC-MS/MS approach. 32,33 For database searching of tandem mass spectra charge state deconvolution and deisotoping were not performed. All MS/MS samples were analyzed using SequestSorcerer (Sage-N), and a FASTA-formatted human protein database (Human RefSeq, 2007) was searched.…”

Section: Mass Spectrometry Analysismentioning

confidence: 99%

“…32 Quantitative assessment and comparison of MV protein composition with different stimuli was based on a previously described spectral counting-based approach. 33,35 Immunoblotting MVs were lysed in 4 ϫ Laemmli sample buffer, boiled, run on 10% (wt/vol) polyacrylamide gels and transferred to nitrocellulose membranes. After blocking for 1 hour in PBS containing 5% albumin and 0.1% (wt/vol) Tween 20, blots were incubated with anti-lactoferrin polyclonal antibody in 1:1000 dilution or anti-␤-actin mAb (both from Sigma-Aldrich) in 1:10 000 or anti-MPO antibody (Cell Signaling, Danvers) in 1:500 dilution in PBS containing 5% ovalbumin.…”

Section: Mass Spectrometry Analysismentioning

confidence: 99%

See 1 more Smart Citation

Antibacterial effect of microvesicles released from human neutrophilic granulocytes

Tímár

Lörincz

Csépányi-Kömi

et al. 2013

Blood

Self Cite

189

267

View full text Add to dashboard Cite

Key Points• Neutrophilic granulocytes stimulated with opsonized particles produce microvesicles (MVs) that are able to impair bacterial growth.• Antibacterial effect correlates with number and size of aggregates between bacteria and MVs and depends on cytoskeletal reorganization of MVs.Cell-derived vesicles represent a recently discovered mechanism for intercellular communication. We investigated their potential role in interaction of microbes with host organisms. We provide evidence that different stimuli induced isolated neutrophilic granulocytes to release microvesicles with different biologic properties. Only opsonized particles initiated the formation of microvesicles that were able to impair bacterial growth. The antibacterial effect of neutrophil-derived microvesicles was independent of production of toxic oxygen metabolites and opsonization or engulfment of the microbes, but depended on ␤ 2 integrin function, continuous actin remodeling, and on the glucose supply. Neutrophil-derived microvesicles were detected in the serum of healthy donors, and their number was significantly increased in the serum of bacteremic patients. We propose a new extracellular mechanism to restrict bacterial growth and dissemination. IntroductionCell-derived vesicles (such as exosomes, ectosomes, microvesicles, shedding microvesicles, and microparticles) represent a recently discovered mechanism for cell-cell communication. [1][2][3] Exosomes are small (50-100 nm) vesicles released from multivesicular bodies. 4 They are involved in antigen presentation [5][6][7] and cell-tocell transfer of receptors 8 or RNA, 9,10 thereby influencing or reprogramming neighboring cells and often promoting tumorigenesis. 8,11 Exosomes also play a role in host defense against microorganisms: tracheobronchial epithelial cells produce exosome-like vesicles with antiviral activity, 12 and macrophage-derived exosomes are able to transfer pathogen-associated molecular patterns of opportunistic intracellular pathogens to uninfected cells. 13 Larger vesicles, called microvesicles (MVs) or microparticles express tissue factor on their surface that is capable of initiating coagulation. 14 Both exosomes and MVs of different cellular origin were detected in various body fluids and selective enrichment was related to specific diseases. [15][16][17][18][19] Neutrophilic granulocytes (PMNs) play a critical role in innate immune mechanisms by engulfing, killing, and degrading various microorganisms. PMNs produce larger vesicles (named by the authors alternatively as ectosomes, microparticles, or MVs) after incubation with various stimuli. [19][20][21][22] Microparticles obtained from PMNs stimulated by chemotactic agents or phorbol esters activated cytokine (IL-6) secretion from endothelial cells 23 and platelets, 24 thereby contributing to the procoagulant effect of leukocytederived microparticles. 25 Chemotactic peptide-induced PMNectosomes increase the secretion of the anti-inflammatory cytokine transforming growth factor ␤ 26 and interfere with the maturatio...

show abstract

“…High-probability peptide and protein assignments were made using Peptide and Protein Prophet algorithms [85]. Abundance of each identified protein was determined by normalizing the number of unique spectral counts matching to the protein by its predicted molecular weight, termed the protein abundance factor [5,86,87]. Cytokine production by unstimulated ABIN1 WTexpressing podocytes was defined as the normal cytokine secretome and was compared to the ABIN1 WT stimulated and both stimulated and non-stimulated ABIN1 [D472N] dataset to identify changes to the normal secretome of these cells.…”

mentioning

confidence: 99%

ABIN1 in the pathogenesis of Glomerulonephritis and the novel polocyte-neutrophil proinflammatory axis.

Korte¹

View full text Add to dashboard Cite

Quantitative mass spectrometry of diabetic kidney tubules identifies GRAP as a novel regulator of TGF-β signaling

Cited by 29 publications

References 79 publications

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Antibacterial effect of microvesicles released from human neutrophilic granulocytes

ABIN1 in the pathogenesis of Glomerulonephritis and the novel polocyte-neutrophil proinflammatory axis.

Contact Info

Product

Resources

About