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

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 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 signaling via protein inhibitor of activated duanyu18133 (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 duanyu18133 was highly up-regulated compared with that of total 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 duanyu18133 was enhanced in tachypaced HL-1 cells. These data indicate that tachypacing decreased ATBF1, leading to enhanced duanyu18133 DNA-binding activity due to the reduced formation of a binary complex of ATBF1 and PIAS3.

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