Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence

Research output: Contribution to journalArticle

Authors

  • Z Varecza
  • K Kvell
  • G Talaber
  • G Miskei
  • V Csongei
  • D Bartis
  • JE Pongracz

Colleges, School and Institutes

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 naive 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. PKC delta 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 beta-catenin dependent signalling in TECs contribute to the initiation of thymic senescence. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Details

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalMechanisms of Ageing and Development
Volume132
Issue number5
Publication statusPublished - 1 May 2011

Keywords

  • PKC delta, Thymic epithelium, Wnt signalling, Thymic atrophy