Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Zigrino P

PROVIDER: S-EPMC4946792 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Zigrino Paola P Brinckmann Jürgen J Niehoff Anja A Lu Yinhui Y Giebeler Nives N Eckes Beate B Kadler Karl E KE Mauch Cornelia C

The Journal of investigative dermatology 20160409 8

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 ...[more]

PMID: 27066886

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Dataset Information

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

Publications

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

Similar Datasets

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