کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6074494 1203487 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleConnective TissueFibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Original ArticleConnective TissueFibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin
چکیده انگلیسی

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-14Sf-/-). 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-14Sf-/- mice without an increase in collagen fibril diameters. However, bleomycin-induced fibrosis in skin proceeded in a comparable manner in MMP-14Sf+/+ and MMP-14Sf-/- mice, but resolution over time was impaired in MMP-14Sf-/- mice. Increased accumulation of collagen type I was detected in MMP-14Sf-/- 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-14Sf-/- 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 136, Issue 8, August 2016, Pages 1575-1583
نویسندگان
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