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

Mirastschijski, Ursula, Lupse, Blaz, Maedler, Kathrin, Sarma, Bhavishya, Radtke, Arlo, Belge, Gazanfer, Dorsch, Martina, Wedekind, Dirk, McCawley, Lisa J, Boehm, Gabriele
et al (show 4 more authors) (2019) Matrix Metalloproteinase-3 is Key Effector of TNF-alpha-Induced Collagen Degradation in Skin. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20 (20). E5234-.

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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.

Item Type: Article
Uncontrolled Keywords: extracellular matrix, inflammation, cytokines, proteinases, interstitial collagens
Depositing User: Symplectic Admin
Date Deposited: 07 Nov 2019 10:33
Last Modified: 19 Jan 2023 00:20
DOI: 10.3390/ijms20205234
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