クボクラ（イシカワ）　マユミ   Ishikawa-Kubokura Mayumi   窪倉（石川）　真由美    所属   東邦大学  医学部 医学科（大森病院）    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Role of growth hormone signaling pathways in the development of atherosclerosis.
掲載誌名	正式名：Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
掲載区分	国外
巻・号・頁	53-54,pp.101334-101334
著者・共著者	Mayumi Ishikawa,Junko Toyomura,Takashi Yagi,Koji Kuboki,Toshisuke Morita,Hitoshi Sugihara,Takahisa Hirose,Shiro Minami,Gen Yoshino
担当区分	筆頭著者
発行年月	2020/07/19
概要	OBJECTIVE: The direct actions of growth hormone (GH) in the development of atherosclerosis are unclear. The goal of this study was to characterize GH-induced changes in expression of signaling pathway elements and other proteins that may be related to atherosclerosis. METHODS: Human umbilical vein endothelial cells (HUVEC) and THP-1, a human acute monocytic leukemia cell line, were stimulated by exposure to 10-9 M or 10-8 M human GH with or without pretreatment with a mitogen-activated protein kinase kinase (MEK) 1 inhibitor. Levels of transcripts encoding vascular cell adhesion molecule (VCAM) -1, E-selectin, monocyte chemotactic protein (MCP-1), interleukin (IL) -6, and IL-8 were investigated by reverse transcription (RT) -PCR. For the quantitative adhesion assay, THP-1 cells or human primary monocytes were fluorescently labeled with 3'-O-acetyl-2',7'-bis(carboxyethyl) -4 diacetoxymethyl ester (BCECF/AM). HUVEC treated with human GH were co-incubated with BCECF-labeled THP-1 cells. One hour later, the number of BCECF-labeled THP-1 cells was assessed. An equivalent experiment was performed using BCECF-labeled primary monocytes, and the number of monocytes adhering to HUVEC was counted. RESULTS: Treatment with hGH increased the levels of E-selectin- and VCAM-1-encoding mRNAs in HUVEC. This effect was attenuated by pretreatment with a MEK1 inhibitor. Furthermore, hGH treatment increased adhesion of BCECF-labeled THP-1 cells or primary monocytes to HUVEC, and this effect was attenuated by pretreatment with a MEK1 inhibitor. CONCLUSIONS: VCAM-1 and E-selectin expression was stimulated by GH via the mitogen-activated protein kinase pathway, resulting in augmented adhesion of THP-1 cells and monocytes to HUVEC. These data suggested that GH directly stimulates the development of atherosclerosis.
DOI	10.1016/j.ghir.2020.101334
PMID	32721858