Expression of collagen VI α5 and α6 chains in human muscle and in Duchenne muscular dystrophy-related muscle fibrosis

Patrizia Sabatelli, Francesca Gualandi, Sudheer Kumar Gara, Paolo Grumati, Alessandra Zamparelli, Elena Martoni, Camilla Pellegrini, Luciano Merlini, Alessandra Ferlini, Paolo Bonaldo, Nadir Mario Maraldi, Mats Paulsson, Stefano Squarzoni, Raimund Wagener

Research output: Contribution to journalArticle

Abstract

Collagen VI is a major extracellular matrix (ECM) protein with a critical role in maintaining skeletal muscle functional integrity. Mutations in COL6A1, COL6A2 and COL6A3 genes cause Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy, and Myosclerosis. Moreover, Col6a1 -/- mice and collagen VI deficient zebrafish display a myopathic phenotype. Recently, two additional collagen VI chains were identified in humans, the α5 and α6 chains, however their distribution patterns and functions in human skeletal muscle have not been thoroughly investigated yet. By means of immunofluorescence analysis, the α6 chain was detected in the endomysium and perimysium, while the α5 chain labeling was restricted to the myotendinous junctions. In normal muscle cultures, the α6 chain was present in traces in the ECM, while the α5 chain was not detected. In the absence of ascorbic acid, the α6 chain was mainly accumulated into the cytoplasm of a sub-set of desmin negative cells, likely of interstitial origin, which can be considered myofibroblasts as they expressed α-smooth muscle actin. TGF-β1 treatment, a pro-fibrotic factor which induces trans-differentiation of fibroblasts into myofibroblasts, increased the α6 chain deposition in the extracellular matrix after addition of ascorbic acid. In order to define the involvement of the α6 chain in muscle fibrosis we studied biopsies of patients affected by Duchenne Muscular Dystrophy (DMD). We found that the α6 chain was dramatically up-regulated in fibrotic areas where, in contrast, the α5 chain was undetectable. Our results show a restricted and differential distribution of the novel α6 and α5 chains in skeletal muscle when compared to the widely distributed, homologous α3 chain, suggesting that these new chains may play specific roles in specialized ECM structures. While the α5 chain may have a specialized function in tissue areas subjected to tensile stress, the α6 chain appears implicated in ECM remodeling during muscle fibrosis.

Original languageEnglish
Pages (from-to)187-196
Number of pages10
JournalMatrix Biology
Volume31
Issue number3
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Duchenne Muscular Dystrophy
Extracellular Matrix
Fibrosis
Collagen
Muscles
Skeletal Muscle
Myofibroblasts
Ascorbic Acid
Desmin
Extracellular Matrix Proteins
Zebrafish
Fluorescent Antibody Technique
Smooth Muscle
Actins
Cytoplasm
Fibroblasts
Phenotype
Biopsy
Mutation
Genes

Keywords

  • Collagen VI
  • Duchenne muscular dystrophy
  • Fibrosis
  • Myotendinous junctions
  • Skeletal muscle

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Expression of collagen VI α5 and α6 chains in human muscle and in Duchenne muscular dystrophy-related muscle fibrosis. / Sabatelli, Patrizia; Gualandi, Francesca; Gara, Sudheer Kumar; Grumati, Paolo; Zamparelli, Alessandra; Martoni, Elena; Pellegrini, Camilla; Merlini, Luciano; Ferlini, Alessandra; Bonaldo, Paolo; Maraldi, Nadir Mario; Paulsson, Mats; Squarzoni, Stefano; Wagener, Raimund.

In: Matrix Biology, Vol. 31, No. 3, 04.2012, p. 187-196.

Research output: Contribution to journalArticle

Sabatelli, P, Gualandi, F, Gara, SK, Grumati, P, Zamparelli, A, Martoni, E, Pellegrini, C, Merlini, L, Ferlini, A, Bonaldo, P, Maraldi, NM, Paulsson, M, Squarzoni, S & Wagener, R 2012, 'Expression of collagen VI α5 and α6 chains in human muscle and in Duchenne muscular dystrophy-related muscle fibrosis', Matrix Biology, vol. 31, no. 3, pp. 187-196. https://doi.org/10.1016/j.matbio.2011.12.003
Sabatelli, Patrizia ; Gualandi, Francesca ; Gara, Sudheer Kumar ; Grumati, Paolo ; Zamparelli, Alessandra ; Martoni, Elena ; Pellegrini, Camilla ; Merlini, Luciano ; Ferlini, Alessandra ; Bonaldo, Paolo ; Maraldi, Nadir Mario ; Paulsson, Mats ; Squarzoni, Stefano ; Wagener, Raimund. / Expression of collagen VI α5 and α6 chains in human muscle and in Duchenne muscular dystrophy-related muscle fibrosis. In: Matrix Biology. 2012 ; Vol. 31, No. 3. pp. 187-196.
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