Browsing by Author "Chen, Yuwen"

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    BMP10 preserves cardiac function through its dual activation of SMAD-mediated and STAT3-mediated pathways
    (Elsevier, 2019-12-27) Qu, Xiuxia; Liu, Ying; Cao, Dayan; Chen, Jinghai; Liu, Zhuo; Ji, Hongrui; Chen, Yuwen; Zhang, Wenjun; Zhu, Ping; Xiao, Deyong; Li, Xiaohui; Shou, Weinian; Chen, Hanying; Pediatrics, School of Medicine
    Bone morphogenetic protein 10 (BMP10) is a cardiac peptide growth factor belonging to the transforming growth factor β superfamily that critically controls cardiovascular development, growth, and maturation. It has been shown that BMP10 elicits its intracellular signaling through a receptor complex of activin receptor-like kinase 1 with morphogenetic protein receptor type II or activin receptor type 2A. Previously, we generated and characterized a transgenic mouse line expressing BMP10 from the α-myosin heavy chain gene promoter and found that these mice have normal cardiac hypertrophic responses to both physiological and pathological stimuli. In this study, we report that these transgenic mice exhibit significantly reduced levels of cardiomyocyte apoptosis and cardiac fibrosis in response to a prolonged administration of the β-adrenoreceptor agonist isoproterenol. We further confirmed this cardioprotective function with a newly generated conditional Bmp10 transgenic mouse line, in which Bmp10 was activated in adult hearts by tamoxifen. Moreover, the intraperitoneal administration of recombinant human BMP10 was found to effectively protect hearts from injury, suggesting potential therapeutic utility of using BMP10 to prevent heart failure. Gene profiling and biochemical analyses indicated that BMP10 activates the SMAD-mediated canonical pathway and, unexpectedly, also the signal transducer and activator of transcription 3 (STAT3)-mediated signaling pathway both in vivo and in vitro Additional findings further supported the notion that BMP10's cardioprotective function likely is due to its dual activation of SMAD- and STAT3-regulated signaling pathways, promoting cardiomyocyte survival and suppressing cardiac fibrosis.
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    The Role of Tbx20 in Cardiovascular Development and Function
    (Frontiers Media, 2021-01-28) Chen, Yuwen; Xiao, Deyong; Zhang, Lu; Cai, Chen-Leng; Li, Bai-Yan; Liu, Ying; Pediatrics, School of Medicine
    Tbx20 is a member of the Tbx1 subfamily of T-box-containing genes and is known to play a variety of fundamental roles in cardiovascular development and homeostasis as well as cardiac remodeling in response to pathophysiological stresses. Mutations in TBX20 are widely associated with the complex spectrum of congenital heart defects (CHDs) in humans, which includes defects in chamber septation, chamber growth, and valvulogenesis. In addition, genetic variants of TBX20 have been found to be associated with dilated cardiomyopathy and heart arrhythmia. This broad spectrum of cardiac morphogenetic and functional defects is likely due to its broad expression pattern in multiple cardiogenic cell lineages and its critical regulation of transcriptional networks during cardiac development. In this review, we summarize recent findings in our general understanding of the role of Tbx20 in regulating several important aspects of cardiac development and homeostasis and heart function.