title: Pax8 plays a pivotal role in regulation of cardiomyocyte growth and senescence.
abstract: Congenital heart disease (CHD) is a worldwide health problem, particularly in young populations. In spite of the advancement and progress in medical research and technology, the underlying causative factors and mechanisms of CHD still remain unclear. Bone morphogenetic protein receptor IA (ALK3) mediates the development of ventricular septal defect (VSD). We have recently found that paired box gene 8 (Pax8) may be the downstream molecule of ALK3. Paired box gene 8 plays an essential role in VSD, and apoptosis and proliferation imbalance leads to septal dysplasia. Recent studies have also disclosed that cellular senescence also participates in embryonic development. Whether programmed senescence exists in cardiac organogenesis has not ever been reported. We hypothesized that together with various biological processes, such as apoptosis, enhanced cellular senescence may occur actively in the development of Pax8 null mice murine hearts. In H9C2 myogenic cells, Pax8 overexpression can rescue caspase-dependent apoptosis induced by ALK3 silencing. Senescent cells and senescence-associated mediators in Pax8 knockout hearts increased compared with the wild-type ones in an age-dependent manner. These results suggest that Pax8 maybe the downstream molecule of ALK3, it mediates the murine heart development perhaps via cellular senescence, which may serve as a mechanism that compensates for the cell loss via apoptosis in heart development.
authors.affiliation: Division of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Division of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Deye
authors.initials: D
authors.lastname: Yang
authors.affiliation: The University of Texas School of Medicine at Houston, Houston, TX, USA.
authors.forename: Yong-jian
authors.initials: YJ
authors.lastname: Geng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence; D018507:Gene Expression Regulation, Developmental; D006345:Heart Septal Defects, Ventricular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D000072636:PAX8 Transcription Factor / Q000172:deficiency / Q000235:genetics*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000072636:PAX8 Transcription Factor; C499496:Pax8 protein, mouse; D034741:RNA, Small Interfering; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: ALK3; Pax8; apoptosis; senescence; ventricular septal defect