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    Por favor, use este identificador para citar o enlazar este ítem:https://uvadoc.uva.es/handle/10324/52280

    Título
    Topical application of TGF-β-activating peptide, KRFK, prevents inflammatory manifestations in the TSP-1-deficient mouse model of chronic ocular inflammation
    Autor
    Soriano Romani, LauraAutoridad UVA Orcid
    Contreras Ruiz, Laura
    López García, Antonio
    Diebold Luque, María YolandaAutoridad UVA Orcid
    Masli, Sharmila
    Año del Documento
    2019
    Editorial
    MDPI
    Descripción
    Producción Científica
    Documento Fuente
    International Journal of Molecular Sciences, 2019, vol. 20, n. 1, p. 9.
    Zusammenfassung
    Chronic inflammation of the ocular surface poses a risk of vision impairment. The understanding of the molecular mechanisms that are involved in the inflammatory response is critical to identify novel molecular targets. Recently, thrombospondin-1 (TSP-1) has emerged as a key player in ocular surface homeostasis that efficiently activates the TGF-β2 isoform that is predominantly expressed in the ocular mucosa. Here, the potential of the peptide derived from TSP-1 (KRFK), that can activate TGF-β, is proposed as a potentially applicable therapeutic for chronic ocular surface inflammatory disorders. Our in vitro results confirm that the chosen peptide activates TGF-β, reducing the expression of co-stimulatory molecules on dendritic cells, driving them towards a tolerogenic phenotype. For the in vivo studies, the TSP-1−/− mouse is used as a pre-clinical model of chronic ocular inflammation. We observe that the topical application of KRFK alters the peripheral balance of effectors by reducing the proportion of pathogenic Th1 and Th17 cells while increasing Treg cell proportion in cervical lymph nodes. In line with these findings, the development of chronic ocular surface inflammation is significantly prevented in KRFK-treated TSP-1−/− mice, as assessed by clinical parameters and inflammatory cytokine expression in conjunctival and lacrimal gland tissues. Together, our results identify the KRFK peptide as a novel therapeutic option to prevent the development of chronic inflammatory manifestations of the ocular surface.
    Materias Unesco
    32 Ciencias Médicas
    Palabras Clave
    Inflammation
    KRFK peptide
    Ocular surface
    Thrombospondin-1
    Transforming growth factor-β
    ISSN
    1661-6596
    Revisión por pares
    SI
    DOI
    10.3390/ijms20010009
    Patrocinador
    Ministerio de Economía, Industria y Competitividad (FEDER-CICYT grant MAT2013-47501-C02-1-R)
    Massachusetts Lions Eye Research Fund (MLERF, S.M.) and NEI grant EY015472 (S.M.)
    Junta de Castilla y León - Fondo Social Europeo (project VA098-12)
    Version del Editor
    https://www.mdpi.com/1422-0067/20/1/9
    Propietario de los Derechos
    © 2018 The Authors
    Idioma
    eng
    URI
    https://uvadoc.uva.es/handle/10324/52280
    Tipo de versión
    info:eu-repo/semantics/publishedVersion
    Derechos
    openAccess
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    • IOBA - Artículos de revista [80]
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    Topical-application-TGF-β-Activating-peptide.pdf
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    Universidad de Valladolid

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