Journal of cellular and molecular medicine, 2011-08, Vol.15 (8), p.1788-1796
2011
Details
- Autor(en) / Beteiligte
- Titel
- Fibrotic response in fibroblasts from congenital disorders of glycosylation
- Ist Teil von
- Journal of cellular and molecular medicine, 2011-08, Vol.15 (8), p.1788-1796
- Ort / Verlag
- Oxford, UK: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Congenital disorders of glycosylation (CDG) are characterized by a generalized underglycosylation of proteins. CDG is associated with multiple symptoms such as psychomotor retardation, hypotonia, hormonal disturbances, liver fibrosis and coagulopathies. The molecular basis of these symptoms is poorly understood considering the large extent of affected glycoproteins. To better understand the cellular responses to protein underglycosylation in CDG, we have investigated the differences in gene expression between healthy control and CDG fibroblasts by transcriptome comparison. This analysis revealed a strong induction of several genes encoding components of the extracellular matrix, such as collagens, COMP, IGFBP5 and biglycan. The extent of this response was confirmed at the protein level by showing increased production of collagen type‐I for example. This fibrotic response of CDG fibroblasts was not paralleled by a differentiation to myofibroblasts and by increased TGF‐β signalling. We could show that the addition of recombinant IGFBP5, one of the induced proteins in CDG, to healthy control fibroblasts increased the production of collagen type‐I to levels similar to those found in CDG fibroblasts. The fibrotic response identified in CDG fibroblasts may account for the elevated tissue fibrosis, which is often encountered in CDG patients.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1582-1838eISSN: 1582-4934DOI: 10.1111/j.1582-4934.2010.01187.xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4373368
- Format
- –
- Schlagworte
- Antibodies, Biglycan - genetics, Biglycan - metabolism, Blotting, Western, Cartilage Oligomeric Matrix Protein, CDG, Cells, Cultured, Cloning, Cluster Analysis, Collagen, Collagen Type I - genetics, Collagen Type I - metabolism, Congenital diseases, Congenital Disorders of Glycosylation - genetics, Congenital Disorders of Glycosylation - metabolism, Congenital Disorders of Glycosylation - pathology, Cytokines, Extracellular matrix, Extracellular Matrix Proteins - genetics, Extracellular Matrix Proteins - metabolism, fibroblast, Fibroblasts, Fibroblasts - drug effects, Fibroblasts - metabolism, Fibroblasts - pathology, Fibrosis, Fibrosis - genetics, Fibrosis - metabolism, Gene expression, Gene Expression Profiling, Genes, Glycoproteins, Glycoproteins - genetics, Glycoproteins - metabolism, Glycosylation, Growth factors, Hepatocytes, Humans, Hybridization, IGFBP5, Insulin-Like Growth Factor Binding Protein 5 - genetics, Insulin-Like Growth Factor Binding Protein 5 - metabolism, Insulin-Like Growth Factor Binding Protein 5 - pharmacology, Insulin-like growth factor-binding protein 5, Intellectual disabilities, Matrilin Proteins, Membranes, Microscopy, Fluorescence, Mutation, Oligonucleotide Array Sequence Analysis, Proteins, Recombinant Proteins - pharmacology, Software, transcriptome, Transcriptomes, Transforming Growth Factor beta - genetics, Transforming Growth Factor beta - metabolism, Transforming Growth Factor beta - pharmacology, Transforming growth factor-b