title: Down-regulation of ATBF1 activates STAT3 signaling via PIAS3 in pacing-induced HL-1 atrial myocytes.
abstract: 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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Buqing
authors.initials: B
authors.lastname: Ni
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Rundi
authors.initials: R
authors.lastname: Qi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors.forename: Dao W
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. Electronic address: chenminglong2001@163.com.
authors.forename: Minglong
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D004558:Electric Stimulation; D055785:Gene Knockdown Techniques; D006325:Heart Atria / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C109279:Pias3 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C489511:Zfhx3 protein, mouse; D004247:DNA
keywords: ATBF1; Atrial fibrillation; Inflammation; STAT3 signaling