Claudin-5 haploinsufficiency exacerbates UVB-induced oedema formation by inducing lymphatic vessel leakage.
Acute exposure of skin to ultraviolet (UV) B irradiation (290-320 nm) leads to epidermal hyperplasia, erythema and oedema formation. We have elucidated that UV irradiation induced the leakiness of cutaneous lymphatic vessels. Although these studies indicated a crucial role of the lymphatic integrity in skin inflammation, the mechanisms underlying its disruption by UVB exposure remain unknown. Here we demonstrated that a vascular-specific tight junction molecule, claudin-5 has an important role in lymphatics and skin inflammation. Claudin-5(+/-) mice, whose claudin-5 expression was greatly downregulated in skin, exacerbates oedema formation and inflammation by a low dose of UVB irradiation. Lymphatic vessels of claudin-5(+/-) mice were markedly enlarged and leaky after low-dose UVB exposure, compared with those of wild-type mice, while the morphology of blood vessels were not different between groups. These results suggest that claudin-5 in the lymphatic tight junction maintains lymphatic integrity and plays a protective role in skin inflammation.
Yuuko
Y
Matsumoto-Okazaki
Mikio
M
Furuse
Kentaro
K
Kajiya
D000818:Animals; D001808:Blood Vessels / Q000473:pathology / Q000528:radiation effects; D062507:Claudin-5 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004487:Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D057895:Haploinsufficiency; D007249:Inflammation / Q000378:metabolism; D042601:Lymphatic Vessels / Q000473:pathology* / Q000528:radiation effects; D008220:Lymphography; D008297:Male; D051379:Mice; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D019108:Tight Junctions / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D062507:Claudin-5; C491511:Cldn5 protein, mouse