RRC ID 67251
Author Kidoya H, Naito H, Muramatsu F, Yamakawa D, Jia W, Ikawa M, Sonobe T, Tsuchimochi H, Shirai M, Adams RH, Fukamizu A, Takakura N.
Title APJ Regulates Parallel Alignment of Arteries and Veins in the Skin.
Journal Dev Cell
Abstract Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well established, but control of parallel arterial-venous 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.
Volume 33(3)
Pages 247-59
Published 2015-5-4
DOI 10.1016/j.devcel.2015.02.024
PII S1534-5807(15)00142-2
PMID 25920569
MeSH Adipokines Animals Apelin Apelin Receptors Arteries / metabolism* Arteries / pathology Body Temperature Regulation / physiology Endothelial Cells / metabolism Endothelium, Vascular / metabolism Glycoproteins / metabolism Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Intracellular Signaling Peptides and Proteins Mice Neovascularization, Physiologic / physiology Receptors, G-Protein-Coupled / metabolism* Skin / blood supply* Skin / metabolism Veins / metabolism*
IF 10.092
Resource
Human and Animal Cells HL60(RCB0041)