Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 132, Issue 5, Pages 249-256Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2011.04.007
Keywords
Wnt signalling; PKC delta; Thymic epithelium; Thymic atrophy
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Funding
- EU [SROP-4.2.2/08/1/2008-0011]
- Wellcome Trust [079415]
- Hungarian Scientific Research Fund [78310]
- Medical Research Council [G1000213, G0401620] Funding Source: researchfish
- MRC [G0401620, G1000213] Funding Source: UKRI
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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.
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