Collagen VI deficiency affects the organization of fibronectin in the extracellular matrix of cultured fibroblasts

Patrizia Sabatelli, Paolo Bonaldo, Giovanna Lattanzi, Paola Braghetta, Natascha Bergamin, Cristina Capanni, Elisabetta Mattioli, Marta Columbaro, Andrea Ognibene, Guglielmina Pepe, Enrico Bertini, Luciano Merlini, Nadir M. Maraldi, Stefano Squarzoni

Research output: Contribution to journalArticle

Abstract

Fibronectin is one of the main components of the extracellular matrix and associates with a variety of other matrix molecules including collagens. We demonstrate that the absence of secreted type VI collagen in cultured primary fibroblasts affects the arrangement of fibronectin in the extracellular matrix. We observed a fine network of collagen VI filaments and fibronectin fibrils in the extracellular matrix of normal murine and human fibroblasts. The two microfibrillar systems did not colocalize, but were interconnected at some discrete sites which could be revealed by immunoelectron microscopy. Direct interaction between collagen VI and fibronectin was also demonstrated by far western assay. When primary fibroblasts from Col6a1 null mutant mice were cultured, collagen VI was not detected in the extracellular matrix and a different pattern of fibronectin organization was observed, with fibrils running parallel to the long axis of the cells. Similarly, an abnormal fibronectin deposition was observed in fibroblasts from a patient affected by Bethlem myopathy, where collagen VI secretion was drastically reduced. The same pattern was also observed in normal fibroblasts after in vivo perturbation of collagen VI-fibronectin interaction with the 3C4 anti-collagen VI monoclonal antibody. Competition experiments with soluble peptides indicated that the organization of fibronectin in the extracellular matrix was impaired by added soluble collagen VI, but not by its triple helical (pepsin-resistant) fragments. These results indicate that collagen VI mediates the three-dimensional organization of fibronectin in the extracellular matrix of cultured fibroblasts.

Original languageEnglish
Pages (from-to)475-486
Number of pages12
JournalMatrix Biology
Volume20
Issue number7
DOIs
Publication statusPublished - 2001

Keywords

  • Bethlem myopathy
  • Collagen VI
  • Extracellular matrix
  • Fibronectin
  • Knockout mice

ASJC Scopus subject areas

  • Molecular Biology

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