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.