Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence

Varecza, Z. and Kvell, Krisztian and Talaber, Gergely and Miskei, Gyorgy and Csöngei, Veronika and Bartis, Domokos and Anderson, Graham and Jenkinson, Eric J. and Pongracz, Judit (2011) Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence. MECHANISMS OF AGEING AND DEVELOPMENT, 132 (5). pp. 249-256. ISSN 0047-6374

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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.

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