ジュウジョウ　ケンタロウ   JUJO Kentaro   重城　健太郎    所属   埼玉医科大学  医学部 総合医療センター　心臓内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Estradiol triggers sonic-hedgehog-induced angiogenesis during peripheral nerve regeneration by downregulating hedgehog-interacting protein
掲載誌名	正式名：LABORATORY INVESTIGATION ISSNコード：00236837
出版社	NATURE PUBLISHING GROUP
巻・号・頁	92(4),532-542頁
著者・共著者	Haruki Sekiguchi,Masaaki Ii,Kentaro Jujo,Marie-Ange Renault,Tina Thorne,Trevor Clarke,Aiko Ito,Toshikazu Tanaka,Ekaterina Klyachko,Yasuhiko Tabata,Nobuhisa Hagiwara,Douglas Losordo
発行年月	2012/04
概要	Both estradiol (E2) and Sonic Hedgehog (Shh) contribute to angiogenesis and nerve regeneration. Here, we investigated whether E2 improves the recovery of injured nerves by downregulating the Shh inhibitor hedgehog-interacting protein (HIP) and increasing Shh-induced angiogenesis. Mice were treated with local injections of E2 or placebo one week before nerve-crush injury; 28 days after injury, nerve conduction velocity, exercise duration, and vascularity were significantly greater in E2-treated mice than in placebo-treated mice. E2 treatment was also associated with higher mRNA levels of Shh, the Shh receptor Patched-1, and the Shh transcriptional target Gli1, but with lower levels of HIP. The E2-induced enhancement of nerve vascularity was abolished by the Shh inhibitor cyclopamine, and the effect of E2 treatment on Shh, Gli1, and HIP mRNA expression was abolished by the E2 inhibitor ICI. Gli-luciferase activity in human umbilical-vein endothelial cells (HUVECs) increased more after treatment with E2 and Shh than after treatment with E2 alone, and E2 treatment reduced HIP expression in HUVECs and Schwann cells without altering Shh expression. Collectively, these findings suggest th
DOI	10.1038/labinvest.2012.6