title: Defective collagen VI α6 chain expression in the skeletal muscle of patients with collagen VI-related myopathies.
abstract: Collagen VI is a non-fibrillar collagen present in the extracellular matrix (ECM) as a complex polymer; the mainly expressed form is composed of α1, α2 and α3 chains; mutations in genes encoding these chains cause myopathies known as Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM). The collagen VI α6 chain is a recently identified component of the ECM of the human skeletal muscle. Here we report that the α6 chain was dramatically reduced in skeletal muscle and muscle cell cultures of genetically characterized UCMD, BM and MM patients, independently of the clinical phenotype, the gene involved and the effect of the mutation on the expression of the "classical" α1α2α3 heterotrimer. By contrast, the collagen VI α6 chain was normally expressed or increased in the muscle of patients affected by other forms of muscular dystrophy, the overexpression matching with areas of increased fibrosis. In vitro treatment with TGF-β1, a potent collagen inducer, promoted the collagen VI α6 chain deposition in the ECM of normal muscle cells, whereas, in cultures derived from collagen VI-related myopathy patients, the collagen VI α6 chain failed to develop a network outside the cells and accumulated in the endoplasmic reticulum. The defect of the α6 chain points to a contribution to the pathogenesis of collagen VI-related disorders.
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy; SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pellegrini
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy; SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sardone
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy; SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Squarzoni
authors.affiliation: Center for Biochemistry, Center for Molecular Medicine (CMMC) and Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Center for Biochemistry, Center for Molecular Medicine (CMMC) and Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wagener
authors.affiliation: Department of Medical Sciences, University of Ferrara, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.affiliation: Department of Medical Sciences, University of Ferrara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Trabanelli
authors.affiliation: Department of Medical Sciences, University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferlini
authors.affiliation: SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy; SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Santi
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: N M
authors.initials: NM
authors.lastname: Maraldi
authors.affiliation: University of Bologna, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Faldini
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy; SC Laboratory of Musculoskeletal Cell Biology, IOR, Bologna, Italy. Electronic address: sabatelli@area.bo.cnr.it.
authors.forename: P
authors.initials: P
authors.lastname: Sabatelli
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism*; D003286:Contracture / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012598:Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C555240:COL6A6 protein, human; D024142:Collagen Type VI; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1
keywords: Collagen VI myopathies; Collagen VI α6 chain; Extracellular matrix; Fibrosis; TGF-β1