@article{oai:shinshu.repo.nii.ac.jp:00042407,
 author = {Arai, Takuma and Sakurai, Takayuki and Kamiyoshi, Akiko and Ichikawa-Shindo, Yuka and Iinuma, Nobuyoshi and Iesato, Yasuhiro and Koyama, Teruhide and Yoshizawa, Takahiro and Uetake, Ryuichi and Yamauchi, Akihiro and Yang, Lei and Kawate, Hisaka and Ogawa, Shinichiro and Kobayashi, Akira and Miyagawa, Shinichi and Shindo, Takayuki},
 issue = {9},
 journal = {PEPTIDES},
 month = {Sep},
 note = {Embryonic stem cells (ESCs) are a useful source for various cell lineages. So far, however, progress toward reconstitution of mature liver morphology and function has been limited. We have shown that knockout mice deficient in adrenomedullin (AM), a multifunctional endogenous peptide, or its receptor-activity modifying protein (RAMP2) die in utero due to poor vascular development and hemorrhage within the liver. In this study, using embryoid bodies (EBs)-culture system, we successfully induced liver sinusoidal endothelial-like cells by modulation of AM-RAMP2. In an EB differentiation system, we found that co-administration of AM and SB431542, an inhibitor of transforming growth factor beta (TGF beta) receptor type 1, markedly enhanced differentiation of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)/stabilin-2-positive endothelial cells. These cells showed robust endocytosis of acetylated low-density lipoprotein (Ac-LDL) and upregulated expression of liver sinusoidal endothelial cells (LSECs)-specific markers, including factor 8 (F8), Fc-gamma receptor 2b (Fcgr2b), and mannose receptor C type 1 (Mrc1), and also possessed fenestrae-like structure, a key morphological feature of LSECs. In RAMP2-null liver, by contrast, LYVE-1 was downregulated in LSECs, and the sinusoidal structure was disrupted. Our findings highlight the importance of AM-RAMP2 signaling for development of LSECs. (C) 2011 Elsevier Inc. All rights reserved., Article, PEPTIDES. 32(9):1855-1865 (2011)},
 pages = {1855--1865},
 title = {Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling},
 volume = {32},
 year = {2011}
}