ヤマニシ　ハルヨ   Haruyo Yamanishi   山西　治代    所属   川崎医科大学  医学部 基礎医学　解剖学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Promotion of lymphatic integrity by angiopoietin-1/Tie2 signaling during inflammation.
掲載誌名	正式名：The American journal of pathology ISSNコード：15252191/00029440
掲載区分	国外
巻・号・頁	180,pp.1273-1282
著者・共著者	Kajiya K, Kidoya H, Sawane M, Matsumoto-Okazaki Y, Yamanishi H, Furuse M, Takakura N
発行年月	2012/03
概要	The cutaneous lymphatic system plays a major role in tissue fluid homeostasis and inflammation of the skin. Although several lymphangiogenic factors are known to be involved in the formation of lymphatic vessels, the molecular mechanisms that maintain lymphatic integrity and control the functional drainage of interstitial fluid and resolution of inflammation remain unknown. Here we show that angiopoietin-1 (Ang1) enhances lymphatic integrity and function during inflammation. Ang1 transgenic mice under the control of keratin-14 (K14-Ang1) showed attenuated edema formation and inflammation after UV B (UVB) exposure. After UVB irradiation, blood vascular permeability was inhibited in K14-Ang1 mice compared with wild-type (WT) mice. Moreover, lymphatic vessels of WT mice were markedly enlarged and leaky in inflamed skin, whereas K14-Ang1 mice showed relatively contracted lymphatic vessels together with enhanced lymphatic vascularization. Expression of endothelial-specific tight junction molecules claudin-5 and zonula occludens protein 1 (ZO-1) was strongly down-regulated in the inflamed lymphatic vessels of UVB-exposed WT mice, whereas down-regulation of both claudin-5 and ZO-1 was blocked in UVB-exposed K14-Ang1 mice. In vitro studies revealed that the stability of lymphatic endothelial cells was enhanced in the presence of Ang1, presumably via up-regulation of claudin-5, as well as ZO-1. Claudin-5 knockdown markedly increased the permeability of lymphatic endothelial cells. Overall, our data strongly support the idea that Ang1/Tie2 signaling promotes lymphatic integrity by modulating tight junction molecule expression during inflammation.