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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.

SUBMITTER: Wu Y

PROVIDER: S-EPMC5125375 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Pax8 plays a pivotal role in regulation of cardiomyocyte growth and senescence.

Wu Yihao Y Zhou Xi X Huang Xiaoyan X Xia Quan Q Chen Zhe Z Zhang Xingwei X Yang Deye D Geng Yong-jian YJ

Journal of cellular and molecular medicine 20160119 4

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, ...[more]

PMID: 26781745

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Pax8 plays a pivotal role in regulation of cardiomyocyte growth and senescence.

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Pax8 plays a pivotal role in regulation of cardiomyocyte growth and senescence.

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