Fibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin

J Invest Dermatol. 2016 Aug;136(8):1575-1583. doi: 10.1016/j.jid.2016.03.036. Epub 2016 Apr 9.


Proteolytic activities in the extracellular matrix by the matrix metalloproteinase (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 the 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-/-) mice without an increase in collagen fibril diameters. However, bleomycin-induced fibrosis in skin proceeded in a comparable manner in MMP-14(Sf+/+) and MMP-14(Sf-/-) mice, but resolution over time was impaired in MMP-14(Sf-/-) mice. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / chemistry
  • Collagen / metabolism*
  • Female
  • Fibroblasts / metabolism*
  • Fibrosis
  • Gene Expression Profiling
  • Homeostasis
  • Inflammation
  • Male
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Mice
  • Mice, Knockout
  • Phenotype
  • Skin / metabolism*
  • Skin / pathology
  • Stress, Mechanical
  • Tensile Strength
  • Wound Healing


  • Mmp14 protein, mouse
  • Bleomycin
  • Collagen
  • Matrix Metalloproteinase 14