Title: Pancreatic beta-cells activate a JunB/ATF3-dependent survival pathway during inflammation
Authors: Gurzov, E N ×
Barthson, J
Marhfour, I
Ortis, F
Naamane, N
Igoillo-Esteve, M
Gysemans, Conny
Mathieu, Chantal
Kitajima, S
Marchetti, P
Orntoft, T F
Bakiri, L
Wagner, E F
Eizirik, D L #
Issue Date: 2012
Publisher: Scientific & Medical Division, Macmillan Press
Series Title: Oncogene vol:31 issue:13 pages:1723-1732
Abstract: Destruction of insulin-producing pancreatic β-cells by local autoimmune inflammation is a hallmark of type 1 diabetes. Histochemical analysis of pancreases from non-obese diabetic mice indicated activation of the transcription factor JunB/AP-1 (activator protein-1) after autoimmune infiltration of the islets. In vitro studies demonstrated that the cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ induce JunB expression as a protective mechanism against apoptosis in both human and rodent β-cells. The gene network affected was studied by microarray analysis showing that JunB regulates nearly 20% of the cytokine-modified β-cell genes, including the transcription factor ATF3. Direct transcriptional induction of ATF3 by JunB is a key event for β-cell survival after TNF-α+IFN-γ treatment. Moreover, pharmacological upregulation of JunB/ATF3 via increased cAMP protected rodent primary β-cells and human islet cells against pro-inflammatory mediators. These results were confirmed in genetically modified islets derived from Ubi-JunB transgenic mice. Our findings identify ATF3 as a novel downstream target of JunB in the survival mechanism of β-cells under inflammatory stress.Oncogene advance online publication, 15 August 2011; doi:10.1038/onc.2011.353.
ISSN: 0950-9232
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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