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

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

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  • Media type: E-Article
  • Title: Matrix metalloproteinase-3 is key effector of TNF-α-induced collagen degradation in skin
  • Contributor: Mirastschijski, Ursula [Author]; Lups̆e, Blaž [Author]; Mädler, Kathrin [Author]; Sarma, Bhavishya [Author]; Radtke, Arlo [Author]; Belge, Gazanfer [Author]; Dorsch, Martina Maria [Author]; Wedekind, Dirk [Author]; McCawley, Lisa J. [Author]; Boehm, Gabriele [Author]; Zier, Ulrich [Author]; Yamamoto, Kazuhiro [Author]; Kelm, Sørge [Author]; Agren, Magnus S. [Author]
  • Published: October 2019
  • Published in: International journal of molecular sciences ; 20(2019), 20, Artikel-ID 5234
  • Language: English
  • DOI: 10.3390/ijms20205234
  • Identifier:
  • Origination:
  • Footnote:
  • 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
  • Access State: Open Access