VGLL4 plays a critical role in heart valve development and homeostasis

  • 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.
Metadaten
Author:Wei Yu, Xueyan Ma, Jinjin Xu, Andreas Wilhelm Heumüller, Zhaoliang Fei, Xue Feng, Xiaodong Wang, Kuo Liu, Jinhui Li, Guizhong Cui, Guangdun Peng, Hongbin Ji, Jinsong Li, Naihe Jing, Hai Song, Zhiqiang Lin, Yun Zhao, Zuoyun Wang, Bin Zhou, Lei Zhang
URN:urn:nbn:de:hebis:30:3-491864
DOI:https://doi.org/10.1371/journal.pgen.1007977
ISSN:1553-7404
ISSN:1553-7390
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30789911
Parent Title (English):PLoS Genetics
Publisher:Public Library of Science
Place of publication:San Francisco, Calif.
Contributor(s):Anthony B. Firulli
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/02/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/03/07
Tag:Alleles; Aortic valve; Apoptosis; Cell proliferation; Endothelial cells; Heart; Homeostasis; Immunostaining
Volume:15
Issue:(2): e1007977
Page Number:19
First Page:1
Last Page:19
Note:
Copyright: © 2019 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS-PPN:448057344
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0