title: Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence.
abstract: Members of the Wnt family of secreted glyco-lipo-proteins affect intrathymic T-cell development and are abundantly secreted by thymic epithelial cells (TECs) that create the specific microenvironment for thymocytes to develop into mature T-cells. During ageing, Wnt expression declines allowing adipoid involution of the thymic epithelium leading to reduced naïve T-cell output. The protein kinase C (PKC) family of serine-threonine kinases is involved in numerous intracellular biochemical processes, including Wnt signal transduction. In the present study, PKCδ expression is shown to increase with age and to co-localise with Wnt receptors Frizzled (Fz)-4 and -6. It is also demonstrated that connective tissue growth factor (CTGF) is a Wnt-4 target gene and is potentially involved in a negative feed-back loop of Wnt signal regulation. Down-regulation of Wnt-4 expression and activation of multiple repressor pathways suppressing β-catenin dependent signalling in TECs contribute to the initiation of thymic senescence.
authors.affiliation: Department of Medical Biotechnology, Institute for Immunology and Biotechnology, University of Pécs, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Varecza
authors.forename: Krisztian
authors.initials: K
authors.lastname: Kvell
authors.forename: Gergely
authors.initials: G
authors.lastname: Talabér
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Miskei
authors.forename: Veronika
authors.initials: V
authors.lastname: Csongei
authors.forename: Domokos
authors.initials: D
authors.lastname: Bartis
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jenkinson
authors.forename: Judit E
authors.initials: JE
authors.lastname: Pongracz
mesh_terms: D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D051745:Protein Kinase C-delta / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C402930:FZD4 protein, human; D051157:Frizzled Receptors; C498581:Fzd4 protein, mouse; C111048:Fzd6 protein, mouse; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D051176:beta Catenin; D051745:Protein Kinase C-delta