2:40 PM - 2:50 PM
[O2-D-PM1-03] Chemically mediated control of angiogenesis via phosphorylation of myosin light chain
Keywords:血管新生、ミオシン軽鎖、ROCK
Angiogenesis is involved in the development and exacerbation of diseases including diabetes and cancer and must be suppressed, whereas it is an essential process for regenerative medicine and tissue transplantation. Therefore, the control of angiogenesis is one of the most important therapeutic strategies. Cytoskeletal regulation by actin-myosin interaction via phosphorylation of myosin light chain 2 (MLC2) plays an important role in the activity of vascular endothelial cells (ECs). MLC2 is phosphorylated by MLC kinase (MLCK) and dephosphorylated by MLC phosphatase (MLCP). In this study, we tried to control angiogenesis by positively or negatively modulating MLC2 phosphorylation with chemicals. Angiogenesis model of human ECs (HUVECs) showed that the formation of vascular networks was enhanced by tautomycetin, while it was inhibited by ML7. The effects of tautomycetin or ML7 correlated with an increase or decreased in phosphorylated MLC2, respectively. These inhibitors affected cell morphology, but not proliferation and migration. Furthermore, analysis of zebrafish vascular development showed that tautomycetin increased vascular length and ML7 inhibited it. This study suggests the possibility of controlling angiogenesis via phosphorylation of MLC2.