APJ Regulates Parallel Alignment of Arteries and Veins in the Skin

作者：Kidoya Hiroyasu; Naito Hisamichi; Muramatsu Fumitaka; Yamakawa Daishi; Jia Weizhen; Ikawa Masahito; Sonobe Takashi; Tsuchimochi Hirotsugu; Shirai Mikiyasu; Adams Ralf H; Fukamizu Akiyoshi; Takakura Nobuyuki^*

来源：Developmental Cell, 2015, 33(3): 247-259.

DOI：10.1016/j.devcel.2015.02.024

Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well established, but control of parallel arterialvenous alignment is unclear. Here we report that arterial-venous alignment in the skin is determined by apelin receptor (APJ) expression in venous ECs. One of the activators of APJ is apelin. We found that apelin is produced by arterial ECs during embryogenesis, induces chemotaxis of venous ECs, and promotes the production of secreted Frizzled-related protein 1 (sFRP1) by APJ(+) ECs. sFRP1 stimulates matrix metalloproteinase production by Ly6B.2(+) neutrophil-like cells located between the arteries and veins, resulting in remodeling of extracellular matrices to support venous displacement. Moreover, using apelin-or APJ-deficient mice, which exhibit arterial-venous disorganization, we found that arterial-venous alignment is involved in thermoregulation, possibly by regulating countercurrent heat exchange. We hypothesize that the evolution of parallel juxtapositional arterial-venous alignment was an adaptation to reduce body heat loss.

• 出版日期2015-5-4