Abstract P795: Activating Transcription Factor 3 Improves Stroke Recovery Through Reduction of Neuronal Damage and Neuroinflammation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zhanqiang Wang ◽  
Peipei Pan ◽  
Rich Liang ◽  
Qifeng Li ◽  
Janothon Pan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ischemic Stroke ◽  
Neuronal Damage ◽  
Stroke Recovery ◽  
Activating Transcription Factor 3 ◽  
Double Labeling ◽  
Activating Transcription Factor ◽  
Adhesive Removal ◽  
Atf3 Expression ◽  
Transcription Factor 3

Background and Purpose: Activating transcription factor 3 (ATF3), a member of the ATF/CREB family, is upregulated in the early phase of various stresses including ischemic stroke. The role of ATF3 in ischemic stroke injury has not been fully elucidated. Hypothesis: ATF3 improves stroke outcomes through reduction of neuronal damage and neuroinflammation. Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was performed in 8-week-old male and female C57BL/6J (WT) and ATF3 knockout (ATF3 -/- ) mice. The sensorimotor functions were analyzed 3 days after pMCAO through adhesive removal and corner tests. Infarct volumes and injured neurons were quantified on Nissl stained and Fluoro-Jade C (FJC) stained sections. The cell-specific expression of ATF3 was analyzed by co-staining ATF3 antibody with antibodies specific to NeuN (Neuron), CD68 (microglia/macrophage) and GFAP (astrocyte). The expression of ATF3 in injured neurons was analyzed by ATF3 and FJC double labeling. Results: ATF3 expression was detected exclusively in neurons in the infarct area 1 day after pMCAO. There were a few ATF3 + CD68 + microglia/macrophages at the peri-infarct regions 2 and 3 days after pMCAO. Almost all FJC + neurons were ATF3 positive. No ATF3 expression was detected in astrocytes. Compared to WT mice, ATF3 -/- mice took longer time to remove the adhesive from their right paws (p<0.001) in adhesive removal test and more left turns in corner test (p<0.001) 3 days after pMCAO. ATF3 -/- mice also had a larger infarct volume (p = 0.014), more FJC + neurons (p=0.002) and CD68 + microglia/macrophages (p=0.003) in the peri-infarct regions than WT mice. Conclusions: Deletion of ATF3 exacerbates neuronal injury, neuroinflammation, and sensorimotor dysfunction in stroke mice, suggesting that upregulation of ATF3 at early stage of stroke improves ischemic stroke recovery through reduction of neuronal damage and neuroinflammation.

scholarly journals Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

2008 ◽  
Vol 158 (5) ◽  
pp. 729-739 ◽  
Author(s):  
Ana Beleza-Meireles ◽  
Virpi Töhönen ◽  
Cilla Söderhäll ◽  
Christian Schwentner ◽  
Christian Radmayr ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mutation Screening ◽  
Activating Transcription Factor 3 ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Genital Development ◽  
Responsive Gene ◽  
Activating Transcription Factor ◽  
Atf3 Expression ◽  
Transcription Factor 3

IntroductionHypospadias is a common inborn error of the genital development, whose complex etiology remains elusive. Defects of the androgen metabolism and activity have been found in a subset of boys with hypospadias. Moreover, the balance between androgens and estrogens seems to be important to the proper male genital development. Activating transcription factor 3 (ATF3), an estrogen responsive gene, has been reported to be expressed during sexual development and up-regulated in hypospadic genital skin. We investigated ATF3 as a candidate gene for hypospadias.Material and methodsGenotyping of eight-tagged single nucleotide polymorphisms (SNP)s was performed in 330 boys with hypospadias and in 380 healthy controls. Screening for mutations in ATF3 was conducted in a subset of boys with hypospadias. ATF3 expression was evaluated in the foreskin of boys with hypospadias and in healthy controls and in the human fetal genitalia by immunohistochemistry.ResultsThree common SNPs, spanning a region of about 16 kb in intron 1 of ATF3, are associated with hypospadias. These SNPs are not linked and their effects are independent. The combination of the three risk SNPs yields the highest significance. Mutation screening identified the gene variant c536A>G in one patient and c817C>T in the 3′-UTR in two other patients. ATF3 expression was evidenced in the developing male urethra.ConclusionsATF3 gene variants influence the risk of hypospadias. Its hormonal responsiveness may underlie this risk effect. But also other ATF3-dependent biological aspects, such as cell survival and death, response to stress stimuli, or the control of epithelial–mesenchymal interactions, may be of importance.

scholarly journals ASBEL–TCF3 complex is required for the tumorigenicity of colorectal cancer cells

2016 ◽  
Vol 113 (45) ◽  
pp. 12739-12744 ◽  
Author(s):  
Kenzui Taniue ◽  
Akiko Kurimoto ◽  
Yasuko Takeda ◽  
Takeshi Nagashima ◽  
Mariko Okada-Hatakeyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Cancer Development ◽  
Activating Transcription Factor 3 ◽  
Colorectal Cancer Cells ◽  
Activating Transcription Factor ◽  
Atf3 Expression ◽  
Transcription Factor 3

Wnt/β-catenin signaling plays a key role in the tumorigenicity of colon cancer. Furthermore, it has been reported that lncRNAs are dysregulated in several steps of cancer development. Here we show that β-catenin directly activates the transcription of the long noncoding RNA (lncRNA) ASBEL [antisense ncRNA in the ANA (Abundant in neuroepithelium area)/BTG3 (B-cell translocation gene 3) locus] and transcription factor 3 (TCF3), both of which are required for the survival and tumorigenicity of colorectal cancer cells. ASBEL interacts with and recruits TCF3 to the activating transcription factor 3 (ATF3) locus, where it represses the expression of ATF3. Furthermore, we demonstrate that ASBEL–TCF3–mediated down-regulation of ATF3 expression is required for the proliferation and tumorigenicity of colon tumor cells. ATF3, in turn, represses the expression of ASBEL. Our results reveal a pathway involving an lncRNA and two transcription factors that plays a key role in Wnt/β–catenin–mediated tumorigenesis. These results may provide insights into the variety of biological and pathological processes regulated by Wnt/β-catenin signaling.

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