However , adherence to laminin was significantly increased (Fig 2)

However , adherence to laminin was significantly increased (Fig 2). observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which CDC7L1 could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases. == Introduction == Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in collagen VI genes (COL6A1, COL6A2 and COL6A3) and is characterised by congenital hypotonia, proximal muscle weakness and distal joint hyperlaxity. Multiple joint contractures and progressive respiratory insufficiency develop over time [1, 2]. In addition to these skeletal features, UCMD patients show a recognisable skin pathology in the form of follicular hyperkeratosis pilaris and abnormal scarring following skin injury mainly in the form of hypertrophic scars and keloids [3, 4]. These constitute a fibrotic process due to the excessive deposition of collagen and other extracellular matrix proteins during the wound healing process [5] and can cause pain and pruritus and significant discomfort in patients that require frequent surgical interventions. Expression of collagen VI mRNA has been shown to increase in the early phases of wound healing and in keloids [6] as well as in other fibrotic processes such as systemic sclerosis [7] suggesting a role in matrix reorganisation, fibrosis and scaring in general. Wound healing of tendons and ligaments is generally similar to that of skin [8]. Collagen VI is abundant in the extracellular matrix of many tissues, where it binds to cell-surface JW74 receptors, integrins [9] and NG2 [10] and to other extracellular matrix (ECM) JW74 components including fibrillar collagens, collagen IV and fibronectin. Via these interactions collagen VI mediates cell adhesion and extracellular matrix organisation [1113]. Collagen also VI triggers intracellular signaling events regulating for instance cell cycle progression [14] and apoptosis [15]. Fibroblasts, which JW74 are the JW74 main source of collagen VI, also synthesise and secrete many other ECM proteins, growth factors, matrix metalloproteinases and other soluble molecules such as chemokines which are necessary to maintain correct tissue homeostasis and function [16]. In order to investigate the effect of collagen VI mutations on skin fibroblasts function and how they may contribute to abnormal scarring and other pathological features seen in collagen VI deficiency we performed global gene expression profiling of skin fibroblasts from healthy controls and UCMD patients. Albeit the recognized differences between skin, muscle and other tissue specific fibroblasts we thought that this approach may also help us shed some light into the mechanisms controlling some of the skeletal changes that are observed in patients with collagen VI defects. Vitamin C is necessary for the hydroxylation of lysyl residues and secretion of different collagen types. In addition , it is a potent antioxidant and has other cellular functions such as promoting cell proliferation, migration, and regulation of gene expression [17]. To find out if collagen VI deficiency has an effect on the fibroblast response to vitamin C we also compared UCMD and healthy fibroblasts that had been previously treated with ascorbic acid. == Materials and Methods == == Ethics Statement == This work has been approved by the Ethical.