UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://www.um.edu.mt/events/scisem/
Email: scisem@um.edu.mt
Abstract form
Title: The cooperation of growth factor signalling and glucocorticoid
transcription regulation in human erythroid progenitor
expansion
Presenter: Victoria Borg
Contact address:
Tel: 79323182
Fax:
Email: victoria.b.borg@gov.mt
Presentation date: 12th May 2014
Abstract
Cooperative signalling between the glucocorticoid receptor and the cytokine
receptors was proven to be central for proper balance between progenitor
proliferation and differentiation. The aim of this study was to identify the mechanism
by which glucocorticoid Dexamethasone (Dex) induces self-renewal capacity in
erythroblasts. Transcription factor (TF) assay was performed to assess the activity
of TFs (NFKB, AP-1, NFAT, CREB, TFIID) in erythroblasts following starvationstimulation experiment using different combinations of cytokines (Epo/Dex/SCF).
This preliminary study showed that Dex cooperates with Epo resulting in the
activation of transcription factors. Microarray data using murine erythroblasts
provided by our collaborator (Erasmus Medical Centre) was analysed and a list of
transcripts that are differentially upregulated in presence of Dex were investigated in
human erythroblasts using gene expression studies. Of interest YWHAH (14-3-3
isoform) was identified as a Dex target. Another isoform of 14-3-3 family – YWHAZ
was also used for gene expression studies. The 14-3-3 family are involved in
various regulatory processes as these are able to interact with many different
proteins. β-catenin is expressed in proliferating cells and since YWHAZ binds to βcatenin preventing its degradation, the expression of β-catenin was studied using
western analysis. Another gene, Zfp36L2, known to promote self-renewal of early
progenitors of red blood cells, was potently induced by Dex in combination with Epo
or SCF. The mechanism by which glucocorticoid receptor activation, together with
enhanced transcription activation of 14-3-3 proteins and Zfp36L2 may be resulting in
enhanced self-renewal of erythroblasts will be discussed.