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Collagen VI disorders: Insights on form and function in the extracellular matrix and beyond
- Source :
- Matrix Biology. :348-367
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Mutations in the three canonical collagen VI genes, COL6A1 , COL6A2 and COL6A3 , cause a spectrum of muscle disease from Bethlem myopathy at the mild end to the severe Ullrich congenital muscular dystrophy. Mutations can be either dominant or recessive and the resulting clinical severity is influenced by the way mutations impact the complex collagen VI assembly process. Most mutations are found towards the N-terminus of the triple helical collagenous domain and compromise extracellular microfibril assembly. Outside the triple helix collagen VI is highly polymorphic and discriminating mutations from rare benign changes remains a major diagnostic challenge. Collagen VI deficiency alters extracellular matrix structure and biomechanical properties and leads to increased apoptosis and oxidative stress, decreased autophagy, and impaired muscle regeneration. Therapies that target these downstream consequences have been tested in a collagen VI null mouse and also in small human trials where they show modest clinical efficacy. An important role for collagen VI in obesity, cancer and diabetes is emerging. A major barrier to developing effective therapies is the paucity of information about how collagen VI deficiency in the extracellular matrix signals the final downstream consequences – the receptors involved and the intracellular messengers await further characterization.
- Subjects :
- 0301 basic medicine
Ullrich congenital muscular dystrophy
Genes, Recessive
Collagen Type VI
medicine.disease_cause
Extracellular matrix
Mice
03 medical and health sciences
Muscular Diseases
Collagen VI
medicine
Extracellular
Animals
Humans
Molecular Targeted Therapy
Receptor
Molecular Biology
Genes, Dominant
Chemistry
Autophagy
Bethlem myopathy
medicine.disease
Extracellular Matrix
Cell biology
030104 developmental biology
Mutation
Oxidative stress
Subjects
Details
- ISSN :
- 0945053X
- Database :
- OpenAIRE
- Journal :
- Matrix Biology
- Accession number :
- edsair.doi.dedup.....c7a5d7ffbdaa2e9892e2f3c08ea253f5