Universität zu Köln

Zigrino, Paola ORCID: 0000-0002-7470-0064, Brinckmann, Juergen, Niehoff, Anja, Lu, Yinhui, Giebeler, Nives, Eckes, Beate, Kadler, Karl E. and Mauch, Cornelia (2016). Fibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin. J. Invest. Dermatol., 136 (8). S. 1575 - 1584. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Proteolytic activities in the extracellular matrix by the matrix metalloproteinase (MMP)-14 have been implicated in the remodeling of collagenous proteins during development. To analyze the function of fibroblast-derived MMP-14 in adult skin homeostasis, we generated mice with inducible deletion of MMP-14 in the dermal fibroblast (MMP-14(Sf-/-)). These mice are smaller and display a fibrosis-like phenotype in the skin. The skin of these mice showed increased stiffness and tensile strength but no altered collagen cross-links. In vivo, we measured a significantly increased amount of collagen type I accumulated in the skin of MMP-14(Sf-/-) mice without an increase in collagen fibril diameters. However, bleomycin-induced fibrosis in skin proceeded in a comparable manner in MMP-14(Sf+/+) and MMP-14(Sf-/-) mice, but resolution over time was impaired in MMP-14(Sf-/-) mice. Increased accumulation of collagen type I was detected in MMP-14(Sf-/-) fibroblasts in culture without significant enhancement of collagen de novo synthesis. This points to a degradative but not synthetic phenotype. In support of this, MMP-14(Sf-/-) fibroblasts lost their ability to process fibrillar collagen type I and to activate proMMP-2. Taken together, these data indicate that MMP-14 expression in fibroblasts plays a crucial role in collagen remodeling in adult skin and largely contributes to dermal homeostasis underlying its pathogenic role in fibrotic skin disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zigrino, Paola UNSPECIFIED orcid.org/0000-0002-7470-0064 UNSPECIFIED Brinckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Lu, Yinhui UNSPECIFIED UNSPECIFIED UNSPECIFIED Giebeler, Nives UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Kadler, Karl E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268948
DOI:	10.1016/j.jid.2016.03.036
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	136
Number:	8
Page Range:	S. 1575 - 1584
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN DERMAL FIBROBLASTS; MATRIX METALLOPROTEINASES; SYSTEMIC-SCLEROSIS; TGF-BETA; FIBROSIS; SCLERODERMA; TURNOVER; ACTIVATION; ANGIOGENESIS; MACROPHAGES Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26894