The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice.

ABSTRACT: DHX15 is a downstream substrate for Akt1, which is involved in key cellular processes affecting vascular biology. Here, we explored the vascular regulatory function of DHX15. Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15^-/- zebrafish also showed downregulation of VEGF-C and reduced formation of lymphatic structures during development. DHX15^+/- mice depicted lower vascular density and impaired lymphatic function postnatally. RNAseq and proteome analysis of DHX15 silenced endothelial cells revealed differential expression of genes involved in the metabolism of ATP biosynthesis. The validation of these results demonstrated a lower activity of the Complex I in the mitochondrial membrane of endothelial cells, resulting in lower intracell

SUBMITTER: Ribera J 

PROVIDER: S-EPMC8519955 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature