Universität zu Köln

Sardone, Francesca, Santi, Spartaco ORCID: 0000-0001-9856-7053, Tagliavini, Francesca ORCID: 0000-0001-5679-2156, Traina, Francesco, Merlini, Luciano ORCID: 0000-0002-1108-1198, Squarzoni, Stefano ORCID: 0000-0001-6538-5923, Cescon, Matilde ORCID: 0000-0001-7138-1857, Wagener, Raimund, Marald, Nadir Mario, Bonaldo, Paolo, Faldini, Cesare and Sabatelli, Patrizia ORCID: 0000-0003-2345-5094 (2016). Collagen VI-NG2 axis in human tendon fibroblasts under conditions mimicking injury response. Matrix Biol., 55. S. 90 - 106. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1569-1802

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Abstract

In response to injury, tendon fibroblasts are activated, migrate to the wound, and contribute to tissue repair by producing and organizing the extracellular matrix. Collagen VI is a microfibrillar collagen enriched in the pericellular matrix of tendon fibroblasts with a potential regulatory role in tendon repair mechanism. We investigated the molecular basis of the interaction between collagen VI and the cell membrane both in tissue sections and fibroblast cultures of human tendon, and analyzed the deposition of collagen VI during migration and myofibroblast trans-differentiation, two crucial events for tendon repair. Tendon fibroblast displayed a collagen VI microfibrillar network closely associated with the cell surface. Binding of collagen VI with the cell membrane was mediated by NG2 proteoglycan, as demonstrated by in vitro perturbation of collagen VI NG2 interaction with a NG2-blocking antibody. Cultures subjected to wound healing scratch assay displayed collagen VI NG2 complexes at the trailing edge of migrating cells, suggesting a potential role in cell migration. In fact, the addition of a NG2-blocking antibody led to an impairment of cell polarization and delay of wound closure. Similar results were obtained after in vitro perturbation of collagen VI extracellular assembly with the 3C4 anti-collagen VI antibody and in collagen VI-deficient tendon cultures of a Ullrich congenital muscular dystrophy patient carrying mutations in COL6A2 gene. Moreover, in vitro treatment with transforming growth factor beta 1 (TGF beta 1) induced a dramatic reduction of NG2 expression, both at protein and mRNA transcript level, and the impairment of collagen VI association with the cell membrane. Instead, collagen VI was still detectable in the extracellular matrix in association with ED-A fibronectin and collagen I, which were strongly induced by TGF beta 1 treatment. Our findings reveal a critical role of the NG2 proteoglycan for the binding of collagen VI to the surface of tendon fibroblasts. By interacting with NG2 proteoglycan and other extracellular matrix proteins, collagen VI regulates fibroblasts behavior and the assembly of tendon matrix, thereby playing a crucial role in tendon repair. (C) 2016 The Authors. Published by Elsevier B.V.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sardone, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Santi, Spartaco UNSPECIFIED orcid.org/0000-0001-9856-7053 UNSPECIFIED Tagliavini, Francesca UNSPECIFIED orcid.org/0000-0001-5679-2156 UNSPECIFIED Traina, Francesco UNSPECIFIED UNSPECIFIED UNSPECIFIED Merlini, Luciano UNSPECIFIED orcid.org/0000-0002-1108-1198 UNSPECIFIED Squarzoni, Stefano UNSPECIFIED orcid.org/0000-0001-6538-5923 UNSPECIFIED Cescon, Matilde UNSPECIFIED orcid.org/0000-0001-7138-1857 UNSPECIFIED Wagener, Raimund UNSPECIFIED UNSPECIFIED UNSPECIFIED Marald, Nadir Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonaldo, Paolo UNSPECIFIED UNSPECIFIED UNSPECIFIED Faldini, Cesare UNSPECIFIED UNSPECIFIED UNSPECIFIED Sabatelli, Patrizia UNSPECIFIED orcid.org/0000-0003-2345-5094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-265864
DOI:	10.1016/j.matbio.2016.02.012
Journal or Publication Title:	Matrix Biol.
Volume:	55
Page Range:	S. 90 - 106
Date:	2016
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1569-1802
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHONDROITIN SULFATE PROTEOGLYCAN; CONGENITAL MUSCULAR-DYSTROPHY; VI-RELATED MYOPATHIES; NG2 PROTEOGLYCAN; TRIPLE-HELIX; EXTRACELLULAR-MATRIX; PERICELLULAR MATRIX; ABNORMAL EXPRESSION; BETHLEM MYOPATHY; ALPHA-6 CHAINS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26586