Linked Life Data

20445556

Source:http://linkedlifedata.com/resource/pubmed/id/20445556

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-8-16
pubmed:abstractText
Systemic sclerosis (SSc) is a disorder of systemic and dermal fibrosis of uncertain etiology. Recently, we found that SSc epidermis is abnormal, taking on an activated phenotype observed during wound healing and tissue repair. As epithelial-fibroblast interactions are important during wound repair and in fibrosis in general, we investigated further the phenotype of the SSc epidermis, and tested whether the SSc epidermis provides a pro-fibrotic stimulus to fibroblasts. In this study we show that in SSc epidermis keratinocyte maturation is delayed, and wound-associated keratins 6 and 16 are induced, in both involved and clinically uninvolved skin. Phosphorylation array analysis revealed induction of stress-induced mitogen-activated protein kinase signaling and mesenchymal feedback through hepatocyte growth factor/c-Met in SSc epidermis. SSc epidermal cells maintained with normal fibroblasts in three-dimensional co-culture were found to stimulate fibroblasts, leading to contractility and connective tissue growth factor expression. These effects depend on elevation of IL-1alpha by the epidermal cells and induction of endothelin-1 and transforming growth factor-beta in fibroblasts. Antagonism of endogenous IL-1alpha using IL-1 receptor antagonist blocked gel contraction by SSc epidermis. We propose that in SSc, epidermal cells are in a persistently activated state and are able to promote dermal fibrosis. These findings are important because biologic therapies could target epithelial-fibroblast interactions in the disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2191-200
pubmed:meshHeading
pubmed-meshheading:20445556-Biopsy, pubmed-meshheading:20445556-Cell Communication, pubmed-meshheading:20445556-Cells, Cultured, pubmed-meshheading:20445556-Coculture Techniques, pubmed-meshheading:20445556-Connective Tissue Growth Factor, pubmed-meshheading:20445556-Endothelin-1, pubmed-meshheading:20445556-Epidermis, pubmed-meshheading:20445556-Epithelial Cells, pubmed-meshheading:20445556-Fibroblasts, pubmed-meshheading:20445556-Fibrosis, pubmed-meshheading:20445556-Humans, pubmed-meshheading:20445556-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:20445556-Interleukin-1alpha, pubmed-meshheading:20445556-Keratin-16, pubmed-meshheading:20445556-Keratin-6, pubmed-meshheading:20445556-Phosphorylation, pubmed-meshheading:20445556-Proto-Oncogene Proteins c-met, pubmed-meshheading:20445556-Scleroderma, Systemic, pubmed-meshheading:20445556-Signal Transduction, pubmed-meshheading:20445556-Stress, Physiological, pubmed-meshheading:20445556-Transforming Growth Factor beta
pubmed:year
2010
pubmed:articleTitle
Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosis.
pubmed:affiliation
Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital Campus, University College Medical School, University College London, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't