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Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin

Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions...

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Autores principales: Mirastschijski, Ursula, Lupše, Blaž, Maedler, Kathrin, Sarma, Bhavishya, Radtke, Arlo, Belge, Gazanfer, Dorsch, Martina, Wedekind, Dirk, McCawley, Lisa J., Boehm, Gabriele, Zier, Ulrich, Yamamoto, Kazuhiro, Kelm, Sørge, Ågren, Magnus S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829232/
https://www.ncbi.nlm.nih.gov/pubmed/31652545
http://dx.doi.org/10.3390/ijms20205234
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author Mirastschijski, Ursula
Lupše, Blaž
Maedler, Kathrin
Sarma, Bhavishya
Radtke, Arlo
Belge, Gazanfer
Dorsch, Martina
Wedekind, Dirk
McCawley, Lisa J.
Boehm, Gabriele
Zier, Ulrich
Yamamoto, Kazuhiro
Kelm, Sørge
Ågren, Magnus S.
author_facet Mirastschijski, Ursula
Lupše, Blaž
Maedler, Kathrin
Sarma, Bhavishya
Radtke, Arlo
Belge, Gazanfer
Dorsch, Martina
Wedekind, Dirk
McCawley, Lisa J.
Boehm, Gabriele
Zier, Ulrich
Yamamoto, Kazuhiro
Kelm, Sørge
Ågren, Magnus S.
author_sort Mirastschijski, Ursula
collection PubMed
description Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions mimicked by the addition of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Skin explants from MMP-3 knock-out (KO) mice or from transgenic (TG) mice overexpressing MMP-3 in the skin and their respective wild-type counterparts (WT and WTT) were incubated ex vivo for eight days. The rate of collagen degradation, measured by released hydroxyproline, was reduced (p < 0.001) in KO skin explants compared to WT control skin but did not differ (p = 0.47) between TG and WTT skin. Treatment with the MMP inhibitor GM6001 reduced hydroxyproline media levels from WT, WTT and TG but not from KO skin explants. TNF-α increased collagen degradation in the WT group (p = 0.0001) only. More of the active form of MMP-13 was observed in the three MMP-3 expressing groups (co-incubation with receptor-associated protein stabilized MMP-13 subforms and enhanced detection in the media). In summary, the innate level of MMP-3 seems responsible for the accelerated loss of cutaneous collagen under inflammatory conditions, possibly via MMP-13 in mice.
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spelling pubmed-68292322019-11-18 Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin Mirastschijski, Ursula Lupše, Blaž Maedler, Kathrin Sarma, Bhavishya Radtke, Arlo Belge, Gazanfer Dorsch, Martina Wedekind, Dirk McCawley, Lisa J. Boehm, Gabriele Zier, Ulrich Yamamoto, Kazuhiro Kelm, Sørge Ågren, Magnus S. Int J Mol Sci Article Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions mimicked by the addition of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Skin explants from MMP-3 knock-out (KO) mice or from transgenic (TG) mice overexpressing MMP-3 in the skin and their respective wild-type counterparts (WT and WTT) were incubated ex vivo for eight days. The rate of collagen degradation, measured by released hydroxyproline, was reduced (p < 0.001) in KO skin explants compared to WT control skin but did not differ (p = 0.47) between TG and WTT skin. Treatment with the MMP inhibitor GM6001 reduced hydroxyproline media levels from WT, WTT and TG but not from KO skin explants. TNF-α increased collagen degradation in the WT group (p = 0.0001) only. More of the active form of MMP-13 was observed in the three MMP-3 expressing groups (co-incubation with receptor-associated protein stabilized MMP-13 subforms and enhanced detection in the media). In summary, the innate level of MMP-3 seems responsible for the accelerated loss of cutaneous collagen under inflammatory conditions, possibly via MMP-13 in mice. MDPI 2019-10-22 /pmc/articles/PMC6829232/ /pubmed/31652545 http://dx.doi.org/10.3390/ijms20205234 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mirastschijski, Ursula
Lupše, Blaž
Maedler, Kathrin
Sarma, Bhavishya
Radtke, Arlo
Belge, Gazanfer
Dorsch, Martina
Wedekind, Dirk
McCawley, Lisa J.
Boehm, Gabriele
Zier, Ulrich
Yamamoto, Kazuhiro
Kelm, Sørge
Ågren, Magnus S.
Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
title Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
title_full Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
title_fullStr Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
title_full_unstemmed Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
title_short Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin
title_sort matrix metalloproteinase-3 is key effector of tnf-α-induced collagen degradation in skin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829232/
https://www.ncbi.nlm.nih.gov/pubmed/31652545
http://dx.doi.org/10.3390/ijms20205234
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