scholarly journals Role of activating transcription factor 3 protein ATF3 in necrosis and apoptosis induced by 5-fluoro-2′-deoxyuridine

FEBS Journal ◽  
2014 ◽  
Vol 281 (7) ◽  
pp. 1892-1900 ◽  
Author(s):  
Akira Sato ◽  
Kentaro Nakama ◽  
Hiroki Watanabe ◽  
Akito Satake ◽  
Akihiro Yamamoto ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activating Transcription Factor 3 ◽  
Activating Transcription Factor ◽  
Transcription Factor 3

Transcriptional regulation of endothelial-to-mesenchymal transition in cardiac fibrosis: role of myocardin-related transcription factor A and activating transcription factor 3

2017 ◽  
Vol 95 (10) ◽  
pp. 1263-1270 ◽  
Author(s):  
Vibhuti Sharma ◽  
Nilambra Dogra ◽  
Uma Nahar Saikia ◽  
Madhu Khullar
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Cardiac Fibrosis ◽  
Activating Transcription Factor 3 ◽  
Mesenchymal Transition ◽  
Related Transcription Factor ◽  
Endothelial To Mesenchymal Transition ◽  
Activating Transcription Factor ◽  
Transcription Factor 3

The etiology of cardiac fibrogenesis is quite diverse, but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined. Myocardin-related transcription factor A facilitates the transcription of cytoskeletal genes by serum response factor during fibrosis; therefore, its specific role in cardiac EndMT might be of importance. Activation of activating transcription factor 3 (ATF-3) during cardiac EndMT is speculative, since ATF-3 responds to a transforming growth factor β (TGF-β) stimulus and controls the expression of the primary epithelial-to-mesenchymal transition markers Snail, Slug, and Twist. Although the role of TGF-β in EndMT-mediated cardiac fibrosis has been established, targeting of the TGF-β ligand has not proven to be a viable anti-fibrotic strategy owing to the broad functional importance of this ligand. Thus, targeting of downstream transcriptional mediators may be a useful therapeutic approach in attenuating cardiac fibrosis. Here, we discuss some of the transcription factors that may regulate EndMT-mediated cardiac fibrosis and their involvement in type 2 diabetes.

Role of activating transcription factor 3 in fructose-induced metabolic syndrome in mice

2018 ◽  
Vol 41 (8) ◽  
pp. 589-597 ◽  
Author(s):  
Chu-Lin Chou ◽  
Ching-Hao Li ◽  
Heng Lin ◽  
Mei-Hui Liao ◽  
Chin-Chen Wu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Transcription Factor ◽  
Activating Transcription Factor 3 ◽  
Activating Transcription Factor ◽  
Transcription Factor 3

scholarly journals Activating transcription factor 3 regulates canonical TGFβ signalling in systemic sclerosis

2015 ◽  
Vol 75 (3) ◽  
pp. 586-592 ◽  
Author(s):  
Tatjana Mallano ◽  
Katrin Palumbo-Zerr ◽  
Pawel Zerr ◽  
Andreas Ramming ◽  
Barbara Zeller ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Systemic Sclerosis ◽  
Cellular Response ◽  
Ectopic Expression ◽  
Activating Transcription Factor 3 ◽  
Dependent Manner ◽  
Reporter Assays ◽  
Activating Transcription Factor ◽  
Transcription Factor 3

BackgroundActivating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element binding (CREB) family of transcription factors, regulates cellular response to stress including oxidative stress. The aim of this study was to analyse the role of ATF3 in fibroblast activation in systemic sclerosis (SSc).MethodsATF3 was analysed by reverse transcription quantitative PCR, western blot and immunohistochemistry. ATF3 knockout fibroblasts and mice were used to study the functional role of ATF3. Knockdown experiments, reporter assays and coimmunoprecipitation were performed to study the effects of ATF3 on Smad and activation protein 1 (AP-1) signalling. The role of c-Jun was analysed by costaining, specific inactivation and coimmunoprecipitation.ResultsTransforming growth factor-β (TGFβ) upregulates the expression of ATF3 in SSc fibroblasts. ATF3-deficient fibroblasts were less sensitive to TGFβ, whereas ectopic expression of ATF3 enhanced the profibrotic effects of TGFβ. Mechanistically, ATF3 interacts with Smad3 directly on stimulation with TGFβ and regulates Smad activity in a c-Jun-dependent manner. Knockout of ATF3 protected mice from bleomycin-induced fibrosis and fibrosis induced by overexpression of a constitutively active TGFβ receptor I. Reporter assays and analyses of the expression of Smad target genes demonstrated that binding of ATF3 regulates the transcriptional activity of Smad3.ConclusionsWe demonstrate for the first time a key role for ATF3 in fibrosis. Knockout of the ATF3 gene reduced the stimulatory effect of TGFβ on fibroblasts by interfering with canonical Smad signalling and protected the mice from experimental fibrosis in two different models. ATF3 might thus be a candidate for molecular targeted therapies for SSc.

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