Claudin-5 haploinsufficiency exacerbates UVB-induced oedema formation by inducing lymphatic vessel leakage

Exp Dermatol. 2012 Jul;21(7):557-9. doi: 10.1111/j.1600-0625.2012.01526.x.

Abstract

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.

Publication types

  • Letter

MeSH terms

  • Animals
  • Blood Vessels / pathology
  • Blood Vessels / radiation effects
  • Claudin-5 / genetics*
  • Claudin-5 / metabolism
  • Down-Regulation
  • Edema / etiology*
  • Edema / metabolism
  • Edema / pathology
  • Haploinsufficiency*
  • Inflammation / metabolism
  • Lymphatic Vessels / pathology*
  • Lymphatic Vessels / radiation effects
  • Lymphography
  • Male
  • Mice
  • Skin / metabolism
  • Skin / pathology*
  • Skin / radiation effects
  • Tight Junctions / metabolism
  • Tight Junctions / radiation effects
  • Ultraviolet Rays / adverse effects*

Substances

  • Claudin-5
  • Cldn5 protein, mouse