Multiple suppression pathways of canonical Wnt signalling control thymic epithelial senescence

作者：Varecza Zoltan; Kvell Krisztian; Talaber Gergely; Miskei Gyorgy; Csongei Veronika; Bartis Domokos; Anderson Graham; Jenkinson Eric J; Pongracz Judit E^*

来源：Mechanisms of Ageing and Development, 2011, 132(5): 249-256.

DOI：10.1016/j.mad.2011.04.007

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

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.

• 出版日期2011-5