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Open AccessArticle

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

1
Center for Biomolecular Interactions Bremen, Department of Biology and Biochemistry, University of Bremen, 28359 Bremen, Germany
2
Faculty of Biology and Biochemistry, University of Bremen, 28359 Bremen, Germany
3
Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany
4
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232-6840, USA
5
Department of General, Visceral and Oncologic Surgery, Klinikum Bremen-Mitte, 28177 Bremen, Germany
6
Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L69 3BX, United Kingdom
7
Digestive Disease Center and Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5234; https://doi.org/10.3390/ijms20205234
Received: 10 October 2019 / Accepted: 17 October 2019 / Published: 22 October 2019
(This article belongs to the Special Issue Matrix Metalloproteinase)
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. View Full-Text
Keywords: extracellular matrix; inflammation; cytokines; proteinases; interstitial collagens extracellular matrix; inflammation; cytokines; proteinases; interstitial collagens
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Mirastschijski, U.; Lupše, B.; Maedler, K.; Sarma, B.; Radtke, A.; Belge, G.; Dorsch, M.; Wedekind, D.; McCawley, L.J.; Boehm, G.; Zier, U.; Yamamoto, K.; Kelm, S.; Ågren, M.S. Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin. Int. J. Mol. Sci. 2019, 20, 5234.

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