Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783465506514141184 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6829232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mirastschijskiursula matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT lupseblaz matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT maedlerkathrin matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT sarmabhavishya matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT radtkearlo matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT belgegazanfer matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT dorschmartina matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT wedekinddirk matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT mccawleylisaj matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT boehmgabriele matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT zierulrich matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT yamamotokazuhiro matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT kelmsørge matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin AT agrenmagnuss matrixmetalloproteinase3iskeyeffectoroftnfainducedcollagendegradationinskin |