Decrease in KAI1/CD82 expression of mural cells in response to angiogenic stimulus

Abstract

Recent studies have highlighted the role of mural cells and tetraspanin molecules in angiogenesis. We and others [1] previously observed that mice that lack KAI1 (also known as CD82), a tetraspanin family member, display higher angiogenic capacity compared to their WT counterpart. Intriguingly, KAI1 was primarily expressed on mural (perivascular) cells in both humans and mice. We next asked if KAI1 expression changes in response to angiogenic stimuli. Angiogenic cytokines reversibly reduced mRNA level of KAI1 in mural cells through Src/PKC-DNMT3A-mediated DNA methylation of Kai1 promoter region. On the other hand, endothelial KAI1 expression showed no significant changes upon angiokine treatment. Furthermore, protein level of KAI1 also was rapidly lowered upon cytokine stimulation through endocytosis. Our study suggests perivascular KAI1 may act as a switch regulating the transition between vessel quiescence and angiogenesis.