An enhancer required for transcription of the Col6a1 gene in muscle connective tissue is induced by signals released from muscle cells

Braghetta, Paola; Ferrari, Alessandra; Fabbro, Carla; Bizzotto, Dario; Volpin, Dino; Bonaldo, Paolo; Bressan, Giorgio M.

doi:10.1016/j.yexcr.2008.08.006

Cited by 30 publications

(30 citation statements)

References 28 publications

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“…Interstitial fibroblasts are the major cell type responsible for its deposition, whereas myogenic cells, which contain factors that can influence ColVI secretion, do not express it (Braghetta et al, 2008;Zou et al, 2008). The crucial role of ColVI in skeletal muscle is emphasized by the fact that mutations in the genes encoding ColVI chains have a causative role in several forms of inherited human muscle diseases, including Bethlem myopathy, Ullrich congenital muscular dystrophy (UCMD) and myosclerosis myopathy (Jöbsis et al, 1996;Camacho Vanegas et al, 2001;Merlini et al, 2008).…”

Section: Skeletal Musclementioning

confidence: 99%

Collagen VI at a glance

Cescon

Gattazzo

Chen

et al. 2015

Journal of Cell Science

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Collagen VI represents a remarkable extracellular matrix molecule, and in the past few years, studies of this molecule have revealed its involvement in a wide range of tissues and pathological conditions. In addition to its complex multi-step pathway of biosynthesis and assembly that leads to the formation of a characteristic and distinctive network of beaded microfilaments in the extracellular matrix, collagen VI exerts several key roles in different tissues. These range from unique biomechanical roles to cytoprotective functions in different cells, including myofibers, chondrocytes, neurons, fibroblasts and cardiomyocytes. Indeed, collagen VI has been shown to exert a surprisingly broad range of cytoprotective effects, which include counteracting apoptosis and oxidative damage, favoring tumor growth and progression, regulating autophagy and cell differentiation, and even contributing to the maintenance of stemness. In this Cell Science at a Glance article and the accompanying poster, we present the current knowledge of collagen VI, and in particular, discuss its relevance in stemness and in preserving the mechanical properties of tissues, as well as its links with human disorders.

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Section: Skeletal Musclementioning

confidence: 99%

Collagen VI at a glance

Cescon

Gattazzo

Chen

et al. 2015

Journal of Cell Science

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283

286

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“…Given the clinical features seen in patients with collagen VI-related myopathies, the tissues in which collagen VI has the most important roles include muscle and tendon. In muscle, the cell source producing collagen VI is the interstitial mesenchymal cell 41 42. In tendons, abundant collagen VI is present in immediate pericellular ECM of the resident tendon fibroblasts 43…”

Section: Molecular Diagnosis Pathogenesis and Therapeutic Avenuesmentioning

confidence: 99%

“…Another report has recently shown that transplanted human adipose-derived stem cells, with phenotypic and functional features of mesenchymal progenitors, secrete collagen VI protein in Col6a1 −/− mice 59. Thus, MSC-based therapy can be an attractive option as transplanted cells are able to self-renew and to differentiate into collagen VI-producing cells in skeletal muscle 41 42…”

Section: Molecular Diagnosis Pathogenesis and Therapeutic Avenuesmentioning

confidence: 99%

Ullrich congenital muscular dystrophy: clinicopathological features, natural history and pathomechanism(s)

Yonekawa

Nishino

2014

Journal of Neurology, Neurosurgery & Psychiatry

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Collagen VI is widely distributed throughout extracellular matrices (ECMs) in various tissues. In skeletal muscle, collagen VI is particularly concentrated in and adjacent to basement membranes of myofibers. Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in either COL6A1, COL6A2 or COL6A3 gene, thereby leading to collagen VI deficiency in the ECM. It is known to occur through either recessive or dominant genetic mechanism, the latter most typically by de novo mutations. UCMD is well defined by the clinicopathological hallmarks including distal hyperlaxity, proximal joint contractures, protruding calcanei, scoliosis and respiratory insufficiency. Recent reports have depicted the robust natural history of UCMD; that is, loss of ambulation by early teenage years, rapid decline in respiratory function by 10 years of age and early-onset, rapidly progressive scoliosis. Muscle pathology is characterised by prominent interstitial fibrosis disproportionate to the relative paucity of necrotic and regenerating fibres. To date, treatment for patients is supportive for symptoms such as joint contractures, respiratory failure and scoliosis. There have been clinical trials based on the theory of mitochondrion-mediated myofiber apoptosis or impaired autophagy. Furthermore, the fact that collagen VI producing cells in skeletal muscle are interstitial mesenchymal cells can support proof of concept for stem cell-based therapy.

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“…Muscle interstitial fibroblasts are the main source of ColVI in the ECM of skeletal muscle . A study revealed that transcription of the Col6a1 gene in skeletal muscle is under the control of a musclespecific enhancer, which is strictly required for activating the expression and synthesis of ColVI in muscle fibroblasts (Braghetta et al 2008). Remarkably, activation of this enhancer requires signals relayed by myogenic cells, whose presence is a prerequisite for inducing the deposition of ColVI by interstitial fibroblasts (Braghetta et al 2008).…”

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confidence: 99%

“…A study revealed that transcription of the Col6a1 gene in skeletal muscle is under the control of a musclespecific enhancer, which is strictly required for activating the expression and synthesis of ColVI in muscle fibroblasts (Braghetta et al 2008). Remarkably, activation of this enhancer requires signals relayed by myogenic cells, whose presence is a prerequisite for inducing the deposition of ColVI by interstitial fibroblasts (Braghetta et al 2008). In vitro and in vivo studies have shown that ColVI is synthesized by interstitial fibroblasts; once released in the ECM, the protein contacts myogenic cells and myofibers Palma et al 2009).…”

mentioning

confidence: 99%

Mitochondrial Dysfunction and Defective Autophagy in the Pathogenesis of Collagen VI Muscular Dystrophies

Bernardi

Bonaldo

2013

Cold Spring Harbor Perspectives in Biology

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Myosclerosis are diseases caused by mutations in the genes encoding the extracellular matrix protein collagen VI. A dystrophic mouse model, where collagen VI synthesis was prevented by targeted inactivation of the Col6a1 gene, allowed the investigation of pathogenesis, which revealed the existence of a Ca 2þ -mediated dysfunction of mitochondria and sarcoplasmic reticulum, and of defective autophagy. Key events are dysregulation of the mitochondrial permeability transition pore, an inner membrane high-conductance channel that for prolonged open times causes mitochondrial dysfunction, and inadequate removal of defective mitochondria, which amplifies the damage. Consistently, the Col6a1 2/2 myopathic mice could be cured through inhibition of cyclophilin D, a matrix protein that sensitizes the pore to opening, and through stimulation of autophagy. Similar defects contribute to disease pathogenesis in patients irrespective of the genetic lesion causing the collagen VI defect. These studies indicate that permeability transition pore opening and defective autophagy represent key elements for skeletal muscle fiber death, and provide a rationale for the use of cyclosporin A and its nonimmunosuppressive derivatives in patients affected by collagen VI myopathies, a strategy that holds great promise for treatment.

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An enhancer required for transcription of the Col6a1 gene in muscle connective tissue is induced by signals released from muscle cells

Cited by 30 publications

References 28 publications

Collagen VI at a glance

Collagen VI at a glance

Ullrich congenital muscular dystrophy: clinicopathological features, natural history and pathomechanism(s)

Mitochondrial Dysfunction and Defective Autophagy in the Pathogenesis of Collagen VI Muscular Dystrophies

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