Down-regulation of ATBF1 activates STAT3 signaling via PIAS3 in pacing-induced HL-1 atrial myocytes

• Published in: Biochemical and biophysical research communications 2014-07, Vol.449 (3), p.278-283
• Main Authors: Jiang, Qi, Ni, Buqing, Shi, Jiaojiao, Han, Zhonglin, Qi, Rundi, Xu, Wenhua, Wang, Dan, Wang, Dao W., Chen, Minglong
• Format: Article
• Language: English
• Subjects: Animals; ATBF1; Atrial fibrillation; Atrial Fibrillation - metabolism; Atrial Fibrillation - physiopathology; Cell Line; DNA - metabolism; Down-Regulation; Electric Stimulation; Gene Knockdown Techniques; Heart Atria - cytology; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Inflammation; Inflammation - metabolism; Mice; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - physiology; Protein Inhibitors of Activated STAT - metabolism; RNA, Small Interfering - genetics; Signal Transduction; STAT3 signaling; STAT3 Transcription Factor - metabolism; Transfection
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.05.041

•Atrial tachypacing induces the decrease of ATBF1 and activation of STAT3 pathway.•The reducing of ATBF1 and activation of STAT3 might contribute to AF generation.•Intervention against these above changes may restore atrial structural remodeling.•These phenomena can be used for treatment monitoring or potential drug targets. Atrial fibrillation (AF) is progressive and is the most common clinical arrhythmia. It is associated with inflammatory changes characterized by signal transducer and activator of transcription 3 (STAT3) signaling. A zinc finger homeobox 3 (ZFHX3, also named AT-motif binding factor 1, ATBF1) gene variant has been found in patients with AF. However, the mechanism by which the ATBF1 leads to inflammation in AF remains unknown. The aim of this study was to investigate whether tachypacing induces a decrease in ATBF1 expression and then activates STAT3 signaling via protein inhibitor of activated STAT3 (PIAS3). Atrial (HL-1 myocytes) cells were cultured in the presence of rapid electrical stimulations. In tachypaced HL-1 cells, we found that ATBF1 and PIAS3 protein levels were decreased, while the level of phosphorylated STAT3 (p-STAT3) was highly up-regulated compared with that of total STAT3. Knockdown of ATBF1 enhanced this trend, while the overexpression of ATBF1 had the opposite effect. A binary complex of ATBF1 and PIAS3 was formed and then the DNA-binding ability of activated STAT3 was enhanced in tachypaced HL-1 cells. These data indicate that tachypacing decreased ATBF1, leading to enhanced STAT3 DNA-binding activity due to the reduced formation of a binary complex of ATBF1 and PIAS3.