VGLL4 plays a critical role in heart valve development and homeostasis

PLoS Genetics
Wei YuLei Zhang

Abstract

Heart valve disease is a major clinical problem worldwide. Cardiac valve development and homeostasis need to be precisely controlled. Hippo signaling is essential for organ development and tissue homeostasis, while its role in valve formation and morphology maintenance remains unknown. VGLL4 is a transcription cofactor in vertebrates and we found it was mainly expressed in valve interstitial cells at the post-EMT stage and was maintained till the adult stage. Tissue specific knockout of VGLL4 in different cell lineages revealed that only loss of VGLL4 in endothelial cell lineage led to valve malformation with expanded expression of YAP targets. We further semi-knockout YAP in VGLL4 ablated hearts, and found hyper proliferation of arterial valve interstitial cells was significantly constrained. These findings suggest that VGLL4 is important for valve development and manipulation of Hippo components would be a potential therapy for preventing the progression of congenital valve disease.

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Citations

Jul 23, 2019·The EMBO Journal·Xue FengLei Zhang
Aug 15, 2020·Frontiers in Oncology·Noritaka Yamaguchi
Jun 6, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Ruya LiuMousumi Moulik
May 26, 2021·Journal of Cardiovascular Translational Research·Ya-Fei LiLian-Sheng Wang
Jun 27, 2021·The FEBS Journal·Jiahong XieHongfeng Jiang
Jul 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiuyun TianYongsheng Gong

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Methods Mentioned

BETA
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transgenic
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fluorescence microscopy

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