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 the researchers 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.
The researchers further semi-knockout YAP in VGLL4 ablated hearts, and found hyper proliferation of arterial valve interstitial cells was significantly constrained.
This is the first in vivo genetic study showing the critical role of the Hippo pathway in regulation of valve remodeling and valve maturation. And the manipulation of Hippo components would be a potential therapy targets for preventing the progression of congenital valve disease.
This study entitled as “VGLL4 plays a critical role in heart valve development and homeostasis” was published in PLoS Genetics on February 21, 2019.
Wei Yu, Zuoyun Wang, Xueyan Ma and her colleagues completed this work who are from the research group led by Prof. Lei Zhang and Prof. Bin Zhou. The work was financially supported by the National Natural Science Foundation of China, National Natural Science, Shanghai Program, “Strategic Priority Research Program” of the Chinese Academy of Sciences, the Youth Innovation Promotion Association Chinese Academy of Sciences and China Postdoctoral Science Foundation.
VGLL4 regulates heart valve development and homeostasis.
Link: Https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007977
AUTHOR CONTACT:
Lei Zhang, Bin Zhou and Zuoyun Wang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
E-mail: rayzhang@sibcb.ac.cn; zhoubin@sibs.ac.cn; wangzuoyun@sibcb.ac.cn.
Appendix：
