Matrix metalloproteinase-3 is key effector of TNF-α-induced collagen degradation in skin

Medientyp: E-Artikel

Titel: Matrix metalloproteinase-3 is key effector of TNF-α-induced collagen degradation in skin

Beteiligte: Mirastschijski, Ursula [Verfasser:in]; Lups̆e, Blaž [Verfasser:in]; Mädler, Kathrin [Verfasser:in]; Sarma, Bhavishya [Verfasser:in]; Radtke, Arlo [Verfasser:in]; Belge, Gazanfer [Verfasser:in]; Dorsch, Martina Maria [Verfasser:in]; Wedekind, Dirk [Verfasser:in]; McCawley, Lisa J. [Verfasser:in]; Boehm, Gabriele [Verfasser:in]; Zier, Ulrich [Verfasser:in]; Yamamoto, Kazuhiro [Verfasser:in]; Kelm, Sørge [Verfasser:in]; Agren, Magnus S. [Verfasser:in]

Erschienen: October 2019

Sprache: Englisch

DOI: 10.3390/ijms20205234

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Beschreibung: 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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