Vascular endothelial growth factor-A mediates ultraviolet B-induced impairment of lymphatic vessel function
Vascular endothelial growth factor-A mediates ultraviolet B-induced impairment of lymphatic vessel function
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DOI：
10.2353/ajpath.2006.060197
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发表时间：
2006-10-01
影响因子：
6
通讯作者：
Detmar, Michael
中科院分区：
文献类型：
--
作者：
Kajiya, Kentaro;Hirakawa, Satoshi;Detmar, Michael
紫外线照射皮肤会导致红斑、表皮增生、血管高通透性和水肿性形成。以往的研究表明，皮肤血管在光损伤的调节中起着关键作用。相比之下，淋巴管在维持组织液平衡中起着至关重要的作用，对UVB辐射的反应仍不清楚。我们在此报道，无论是急性还是慢性UVB照射小鼠皮肤，都会导致淋巴管显著增大。令人惊讶的是，活体淋巴管造影术发现，这些增大的淋巴管在功能上是受损的，并且具有高通透性。在UVB照射的表皮中，血管内皮生长因子-A的表达水平增加，而已知的淋巴管生成因子血管内皮生长因子-C和血管内皮生长因子-D的表达水平没有增加。转基因小鼠表皮靶向过表达VEGF-A导致急性UVB照射后淋巴管增大和渗漏增加，而全身性阻断VEGF-A信号在很大程度上阻止了UVB诱导的淋巴管异常和光损伤。总之，这些发现确定淋巴管是UVB诱导的皮肤光损伤的新靶点，并提示VEGF-A介导了淋巴管功能的损害，从而导致了UVB辐射对皮肤的不良影响。
UVB irradiation of the skin induces erythema, epidermal hyperplasia, vascular hyperpermeability, and edema formation. Previous studies have revealed that the cutaneous blood vasculature plays a critical role in the mediation of photodamage. In contrast, the role of lymphatic vessels, which play an essential role in the maintenance of tissue fluid balance, in the response to UVB irradiation has remained unknown. We report here that both acute and chronic UVB irradiation of murine skin results in prominent enlargement of lymphatic vessels. Surprisingly, these enlarged lymphatic vessels were functionally impaired and hyperpermeable, as detected by intravital lymphangiography. The expression levels of vascular endothelial growth factor (VEGF)-A but not of the known lymphangiogenesis factors VEGF-C or VEGF-D, were enhanced in UVB-irradiated epidermis. Targeted overexpression of VEGF-A in the epidermis of transgenic mice led to increased enlargement and leakage of lymphatic vessels after acute UVB irradiation, whereas systemic blockade of VEGF-A signaling largely prevented lymphatic vessel abnormalities and photodamage induced by UVB. Together, these findings identify lymphatic vessels as novel targets for UVB-induced cutaneous photodamage and suggest that VEGF-A mediates impairment of lymphatic vessel function, thereby contributing to the adverse effects of UVB irradiation on the skin.