Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence

Zoltan Varecza, Krisztian Kvell, Gergely Talabér, Gyorgy Miskei, Veronika Csongei, Domokos Bartis, Graham Anderson, Eric J. Jenkinson, Judit E. Pongracz

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalMechanisms of Ageing and Development
Volume132
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • PKCδ
  • Thymic atrophy
  • Thymic epithelium
  • Wnt signalling

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology

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