A pro-angiogenic and hypoxic zebrafish model as a novel platform for anti-angiogenic drug testing.

ABSTRACT: Zebrafish is a valuable model for antiangiogenic drug testing. We hypothesized that the efficacy of antiangiogenic compounds might vary in hypoxic tissue environments compared to normal tissue. To explore this, we established a chemically induced zebrafish model using DMOG, which inhibits prolyl hydroxylases, and a genetic model by knocking out vhl gene via CRISPR/Cas9 to activate hypoxia signaling. In wild-type larvae, the antiangiogenic drug sorafenib inhibited blood vessel growth. However, in the DMOG model and vhl-/- model, no inhibition occurred in sub-intestinal vessel (SIV) upon sorafenib treatment. Also, gene expression analysis showed that the DMOG induced hypoxia had 20-fold increase in phd3 expression, a marker for hypoxia signaling activation, which rose to 65-fold and 280-fold

SUBMITTER: S V 

PROVIDER: S-EPMC12381926 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature