Print Email Facebook Twitter Extracellular matrix proteins: A positive feedback loop in lung fibrosis? Title Extracellular matrix proteins: A positive feedback loop in lung fibrosis? Author Blaauboer, M.E. Boeijen, F.R. Emson, C.L. Turner, S.M. Zandieh-Doulabi, B. Hanemaaijer, R. Smit, T.H. Stoop, R. Everts, V. Publication year 2014 Abstract Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the development of bleomycin-induced lung fibrosis. We further report in vitro experiments clarifying both the effect of myofibroblast differentiation on this expression and the effect of extracellular elastin on myofibroblast differentiation. Lung fibrosis was induced in female C57Bl/6 mice by bleomycin instillation. Animals were sacrificed at zero to five weeks after fibrosis induction. Collagen synthesized during the week prior to sacrifice was labeled with deuterium. After sacrifice, lung tissue was collected for determination of new collagen formation, microarray analysis, and histology. Human lung fibroblasts were grown on tissue culture plastic or BioFlex culture plates coated with type I collagen or elastin, and stimulated to undergo myofibroblast differentiation by 0-10ng/ml transforming growth factor (TGF)β1. mRNA expression was analyzed by quantitative real-time PCR.New collagen formation during bleomycin-induced fibrosis was highly correlated to gene expression of elastin, type V collagen and tenascin C. At the protein level, elastin, type V collagen and tenascin C were highly expressed in fibrotic areas as seen in histological sections of the lung. Type V collagen and tenascin C were transiently increased. Human lung fibroblasts stimulated with TGFβ1 strongly increased gene expression of elastin, type V collagen and tenascin C. The extracellular presence of elastin increased gene expression of the myofibroblastic markers α smooth muscle actin and type I collagen.The extracellular matrix composition changes dramatically during the development of lung fibrosis. The increased levels of elastin, type V collagen and tenascin C are probably the result of increased expression by fibroblastic cells; reversely, elastin influences myofibroblast differentiation. This suggests a reciprocal interaction between fibroblasts and the extracellular matrix composition that could enhance the development of lung fibrosis. © 2013 International Society of Matrix Biology. Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationHealthHealthy LivingElastinExtracellular matrixLung fibrosisMyofibroblast differentiationTenascin CType V collagen To reference this document use: http://resolver.tudelft.nl/uuid:82f12186-e6fe-4ae5-9144-e5f747e317c4 DOI https://doi.org/10.1016/j.matbio.2013.11.002 TNO identifier 503200 ISSN 1569-1802 Source Matrix Biology, 34, 170-178 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.