Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets.
Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0077430 |
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| author | Sonia Paco Susana G Kalko Cristina Jou María A Rodríguez Joan Corbera Francesco Muntoni Lucy Feng Eloy Rivas Ferran Torner Francesca Gualandi Anna M Gomez-Foix Anna Ferrer Carlos Ortez Andrés Nascimento Jaume Colomer Cecilia Jimenez-Mallebrera |
| author_facet | Sonia Paco Susana G Kalko Cristina Jou María A Rodríguez Joan Corbera Francesco Muntoni Lucy Feng Eloy Rivas Ferran Torner Francesca Gualandi Anna M Gomez-Foix Anna Ferrer Carlos Ortez Andrés Nascimento Jaume Colomer Cecilia Jimenez-Mallebrera |
| author_sort | Sonia Paco |
| collection | DOAJ |
| description | Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered. |
| format | Article |
| id | doaj-art-815aece34f2d4a379f7f4e970f0aec23 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-815aece34f2d4a379f7f4e970f0aec232025-08-20T03:46:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7743010.1371/journal.pone.0077430Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets.Sonia PacoSusana G KalkoCristina JouMaría A RodríguezJoan CorberaFrancesco MuntoniLucy FengEloy RivasFerran TornerFrancesca GualandiAnna M Gomez-FoixAnna FerrerCarlos OrtezAndrés NascimentoJaume ColomerCecilia Jimenez-MallebreraUllrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.https://doi.org/10.1371/journal.pone.0077430 |
| spellingShingle | Sonia Paco Susana G Kalko Cristina Jou María A Rodríguez Joan Corbera Francesco Muntoni Lucy Feng Eloy Rivas Ferran Torner Francesca Gualandi Anna M Gomez-Foix Anna Ferrer Carlos Ortez Andrés Nascimento Jaume Colomer Cecilia Jimenez-Mallebrera Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. PLoS ONE |
| title | Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. |
| title_full | Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. |
| title_fullStr | Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. |
| title_full_unstemmed | Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. |
| title_short | Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets. |
| title_sort | gene expression profiling identifies molecular pathways associated with collagen vi deficiency and provides novel therapeutic targets |
| url | https://doi.org/10.1371/journal.pone.0077430 |
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