Global remodelling of cellular microenvironment due to loss of collagen VII

The mammalian cellular microenvironment is shaped by soluble factors and structural components, the extracellular matrix, providing physical support, regulating adhesion and signalling. A global, quantitative mass spectrometry strategy, combined with bioinformatics data processing, was developed to...

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Bibliographic Details
Published in:Molecular systems biology Vol. 9; no. 1; pp. 657 - n/a
Main Authors: Küttner, Victoria, Mack, Claudia, Rigbolt, Kristoffer TG, Kern, Johannes S, Schilling, Oliver, Busch, Hauke, Bruckner‐Tuderman, Leena, Dengjel, Jörn
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 16.04.2013
John Wiley & Sons, Ltd
EMBO Press
Nature Publishing Group
Springer Nature
Subjects:
Basement Membrane - metabolism
Basement Membrane - pathology
Bioinformatics
Case-Control Studies
Cell adhesion & migration
Cell Communication
Cellular Microenvironment - genetics
Cellular structure
Collagen
Collagen Type VII - deficiency
Collagen Type VII - genetics
Data processing
Dermis - metabolism
Dermis - pathology
disease proteomics
EMBO24
EMBO31
Epidermolysis Bullosa Dystrophica - genetics
Epidermolysis Bullosa Dystrophica - metabolism
Epidermolysis Bullosa Dystrophica - pathology
Extracellular matrix
extracellular matrix (ECM)
Extracellular Matrix - genetics
Extracellular Matrix - pathology
Female
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - pathology
Fragility
Gene Expression
Grants
Growth factors
Humans
Infant
Infant, Newborn
Male
Mass spectrometry
Mass spectroscopy
Metalloproteases - genetics
Metalloproteases - metabolism
MMP14
Mutation
Pathogenesis
Primary Cell Culture
primary human fibroblasts
Protein Processing, Post-Translational
Proteins
Proteomes
Proteomics
Signal transduction
Skin
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
Germany
mass spectrometry
primary human fibroblasts
extracellular matrix (ECM)
MMP14
disease proteomics
ISSN:1744-4292, 1744-4292
Online Access:Get full text
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Summary:The mammalian cellular microenvironment is shaped by soluble factors and structural components, the extracellular matrix, providing physical support, regulating adhesion and signalling. A global, quantitative mass spectrometry strategy, combined with bioinformatics data processing, was developed to assess proteome differences in the microenvironment of primary human fibroblasts. We studied secreted proteins of fibroblasts from normal and pathologically altered skin and their post‐translational modifications. The influence of collagen VII, an important structural component, which is lost in genetic skin fragility, was used as model. Loss of collagen VII had a global impact on the cellular microenvironment and was associated with proteome alterations highly relevant for disease pathogenesis including decrease in basement membrane components, increase in dermal matrix proteins, TGF‐β and metalloproteases, but not higher protease activity. The definition of the proteome of fibroblast microenvironment and its plasticity in health and disease identified novel disease mechanisms and potential targets of intervention. Loss of collagen VII causes recessive dystrophic epidermolysis bullosa . Quantitative proteomics analysis of the extracellular matrix and secretome of human fibroblasts derived from pathologically altered skin reveals a global remodelling of the cellular microenvironment. Synopsis Loss of collagen VII causes recessive dystrophic epidermolysis bullosa . Quantitative proteomics analysis of the extracellular matrix and secretome of human fibroblasts derived from pathologically altered skin reveals a global remodelling of the cellular microenvironment. A global analysis of the microenvironment of human skin fibroblasts was carried out to reveal disease‐related alterations in the extracellular proteome. The loss of collagen VII causes a deregulation of the basement membrane and dermal matrix proteome. Post‐translational modifications of secreted proteins were altered in fibroblasts from recessive dystrophic epidermolysis bullosa samples. Metalloproteases displayed reduced activity and turnover in collagen VII‐deficient cells.
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ISSN:1744-4292
1744-4292
DOI:10.1038/msb.2013.17