title: Global remodelling of cellular microenvironment due to loss of collagen VII.
abstract: 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.
authors.affiliation: School of Life Science-LifeNet, Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Küttner
authors.forename: Claudia
authors.initials: C
authors.lastname: Mack
authors.forename: Kristoffer T G
authors.initials: KT
authors.lastname: Rigbolt
authors.forename: Johannes S
authors.initials: JS
authors.lastname: Kern
authors.forename: Oliver
authors.initials: O
authors.lastname: Schilling
authors.forename: Hauke
authors.initials: H
authors.lastname: Busch
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
mesh_terms: D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002450:Cell Communication; D060833:Cellular Microenvironment / Q000235:genetics*; D024143:Collagen Type VII / Q000172:deficiency / Q000235:genetics*; D020405:Dermis / Q000378:metabolism* / Q000473:pathology; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000235:genetics* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D024143:Collagen Type VII; D016212:Transforming Growth Factor beta; D045726:Metalloproteases