Universität zu Köln

Schonboern, Katrin, Willenborg, Sebastian, Schulz, Jan-Niklas, Imhof, Thomas, Eming, Sabine A., Quondamatteo, Fabio, Brinckmann, Juergen, Niehoff, Anja ORCID: 0000-0002-4165-0929, Paulsson, Mats, Koch, Manuel, Eckes, Beate and Krieg, Thomas (2020). Role of collagen XII in skin homeostasis and repair. Matrix Biol., 94. S. 57 - 77. AMSTERDAM: ELSEVIER. ISSN 1569-1802

Full text not available from this repository.

Abstract

Skin integrity and function depends to a large extent on the composition of the extracellular matrix, which regulates tissue organization. Collagen XII is a homotrimer with short collagenous domains that confer binding to the surface of collagen I-containing fibrils and extended flexible arms, which bind to non-collagenous matrix components. Thereby, collagen XII helps to maintain collagen suprastructure and to absorb stress. Mutant or absent collagen XII leads to reduced muscle and bone strength and lax skin, whereas increased collagen XII amounts are observed in tumor stroma, scarring and fibrosis. This study aimed at uncovering in vivo mechanisms by which collagen XII may achieve these contrasting outcomes. We analyzed skin as a model tissue that contains abundant fibrils, composed of collagen I, III and V with collagen XII decorating their surface, and which is subject to mechanical stress. The impact of different collagen XII levels was investigated in collagen XII-deficient (Col12-KO) mice and in mice with collagen XII overexpression in the dermis (Col12-OE). Unchallenged skin of these mice was histologically inconspicuous, but at the ultrastructural level revealed distinct aberrations in collagen network suprastructure. Repair of excisional wounds deviated from controls in both models by delayed healing kinetics, which was, however, caused by completely different mechanisms in the two mouse lines. The disorganized matrix in Col12-KO wounds failed to properly sequester TGF beta, resulting in elevated numbers of myofibroblasts. These are, however, unable to contract and remodel the collagen XII-deficient matrix. Excess of collagen XII, in contrast, promotes persistence of M1-like macrophages in the wound bed, thereby stalling the wounds in an early inflammatory stage of the repair process and delaying healing. Taken together, we demonstrate that collagen XII is a key component that assists in orchestrating proper skin matrix structure, controls growth factor availability and regulates cellular composition and function. Together, these functions are pivotal for re-establishing homeostasis after injury. (C) 2020 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schonboern, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Willenborg, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Jan-Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Imhof, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Quondamatteo, Fabio UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED orcid.org/0000-0002-4165-0929 UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-309299
DOI:	10.1016/j.matbio.2020.08.002
Journal or Publication Title:	Matrix Biol.
Volume:	94
Page Range:	S. 57 - 77
Date:	2020
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1569-1802
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TISSUE-SPECIFIC EXPRESSION; OLIGOMERIC MATRIX PROTEIN; SHORT SPLICE VARIANTS; EXTRACELLULAR-MATRIX; DIFFERENTIAL EXPRESSION; GRANULATION-TISSUE; MOUSE; FIBROBLASTS; FIBRILS; ABSENCE Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30929