Foxo1 deletion promotes the growth of new lymphatic valves.

ABSTRACT: Patients with congenital lymphedema suffer from tissue swelling in part due to mutations in genes regulating lymphatic valve development. Lymphatic valve leaflets grow and are maintained throughout life in response to oscillatory shear stress (OSS), which regulates gene transcription in lymphatic endothelial cells (LECs). Here, we identified the first transcription factor, Foxo1, that repressed lymphatic valve formation by inhibiting the expression of valve-forming genes. We showed that both embryonic and postnatal ablation of Foxo1 in LECs induced additional valve formation in postnatal and adult mice in multiple tissues. Our quantitative analyses revealed that after deletion, the total number of valves in the mesentery was significantly (P < 0.01) increased in the Foxo1LEC-KO mice compar

SUBMITTER: Scallan JP 

PROVIDER: S-EPMC8279588 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature