Fibroblast-derived MMP-14 regulates collagen homeostasis in adult skin

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Authors

  • Paola Zigrino
  • Jürgen Brinckmann
  • Anja Niehoff
  • Yinhui Lu
  • Nives Giebeler
  • Beate Eckes
  • Karl E Kadler
  • Cornelia Mauch

Research units

Details

Proteolytic activities in the extracellular matrix by the MMP-14 have been implicated in the remodeling of collagenous proteins during development. To analyze the function of fibroblast-derived MMP-14 in adult skin homeostasis we generated mice with inducible deletion of MMP-14 in the dermal fibroblast (MMP-14(Sf-/-)). These mice are smaller and display a fibrosis-like phenotype in skin. The skin of these mice showed increased stiffness and tensile strength, but no altered collagen cross-links. In vivo, we measured a significantly increased amount of collagen type I accumulated in the skin of MMP-14(Sf-/-) without an increase in collagen fibrils diameters. However, bleomycin-induced fibrosis in skin proceeded in a comparable manner in MMP-14(Sf+/+) and MMP-14(Sf-/-), but resolution overtime was impaired in MMP-14(Sf-/-.). Increased accumulation of collagen type I was detected in MMP-14(Sf-/-) fibroblasts in culture without significant enhancement of collagen de novo synthesis. This points to a degradative, but not synthetic phenotype. In support of this, MMP-14(Sf-/-) fibroblasts lost their ability to process fibrillar collagen type I and to activate proMMP-2. Taken together, these data indicate that MMP-14 expression in fibroblasts plays a crucial role in collagen remodeling in adult skin and largely contributes to dermal homeostasis underlying its pathogenic role in fibrotic skin disease.

Original languageEnglish
JournalThe Journal of investigative dermatology
Number of pages34
DOIs
Publication statusPublished - 08.04.2016

ID: 2059863

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