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Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis
Journal article   Open access   Peer reviewed

Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis

Kristen B Long, Carol M Artlett and Elizabeth P Blankenhorn
Matrix biology, v 38, pp 91-100
Sep 2014
DOI: https://doi.org/10.1016/j.matbio.2014.05.002
PMID: 24820199
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.matbio.2014.05.002View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Age Factors Animals Carrier Proteins - metabolism Collagen - physiology Extracellular Matrix - physiology Fibrosis Fluorescent Antibody Technique Hydroxyproline - metabolism Linear Models Mice NLR Family, Pyrin Domain-Containing 3 Protein Scleroderma, Systemic - genetics Scleroderma, Systemic - physiopathology Skin - metabolism Skin - pathology Transforming Growth Factor beta1 - metabolism
The tight skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of the human disease including tight skin, fibrosis, extracellular matrix abnormalities, and reported antinuclear antibodies (ANA). Here we report that Tsk2/+ mice develop excess dermal fibrosis with age, as skin is not significantly fibrotic until 10 weeks, a full eight weeks after the development of the physical tight skin phenotype. Concomitantly with the tight skin phenotype at two weeks of age, Tsk2/+ mice demonstrate increased levels of total transforming growth factor beta 1 (TGF-β1) and excessive accumulation of dermal elastic fibers. The increase in elastic fibers is not responsible for tight skin, however, because Tsk2/+ mice genetically engineered to lack skin elastic fibers nevertheless have tight skin and fibrosis. Finally, about two months after the first measurable increases of total collagen, a portion of Tsk2/+ mice produce ANAs, but at a similar level to wild-type littermates. The timeline of disease development in the Tsk2/+ mouse shows that fibrosis is progressive, with elastic fiber alterations and TGF-β1 over-production occurring at least two months before bona fide fibrosis, that is not dependent on ANA production.

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Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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