Targeted overexpression of Angpt16/angiopoietin-related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B
Targeted overexpression of Angpt16/angiopoietin-related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B
复制标题
皮肤中 Angpt16/血管生成素相关生长因子的靶向过度表达可响应紫外线 B 促进血管生成和淋巴管扩张
DOI：
10.1111/j.1346-8138.2011.01396.x
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发表时间：
2012
期刊：
影响因子：
3.1
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Okazaki H;et al
血管生成是生理组织修复过程所需的，例如皮肤伤口愈合。然而，最近的研究表明，内源性血管生成因子可能会增强实验性紫外线（UV）-B暴露引起的光诱导皮肤变化。血管生成素相关生长因子（AGF），也称为血管生成素样蛋白6（Angptl 6），已知可促进新血管形成和血管通透性过高。重要的是，小鼠中Angptl 6/AGF的表皮过表达促进皮肤中的伤口愈合。然而，仍不清楚Angptl 6/AGF的过表达是否促进响应于UV-B照射的组织修复过程。为了验证这一假设，我们将Angptl 6/AGF转基因小鼠置于急性或慢性UV-B暴露中。令人惊讶的是，转基因小鼠对阈下剂量的UV-B表现出增强的光敏性，而在野生型同窝出生的小鼠中不会诱导皮肤改变。在Angptl 6/AGF转基因小鼠中，在单次暴露于UV-B后观察到血管显著增大，但未观察到表皮变化。在Angptl 6/AGF转基因小鼠中，超过14周的慢性B暴露促进皮肤损伤，而野生型小鼠表现出很少或没有肉眼可见的皮肤改变。除了明显的血管生成和表皮增生外，在UV-B-暴露的Angptl 6/AGF转基因小鼠中观察到真皮淋巴管显著增大。电子显微镜分析进一步显示，Angptl 6/AGF转基因小鼠在慢性UV-B暴露后，真皮中胶原束的数量和大小显著减少。总之，这些结果表明小鼠中Angptl 6/AGF的异位表达可能促进UV-B-诱导的皮肤改变，并且血管生成可能是预防皮肤光老化的治疗靶点。
Angiogenesis is required for physiological tissue repair processes, such as cutaneous wound healing. However, recent studies indicate that endogenous angiogenic factors may enhance photo‐induced skin alterations in response to experimental ultraviolet (UV)‐B exposure. Angiopoietin‐related growth factor (AGF), also known as angiopoietin‐like protein 6 (Angptl6), is known to promote new blood vessel formation and vascular hyperpermeability. Importantly, epidermal overexpression of Angptl6/AGF in mice promotes wound healing in the skin. However, it remains unclear whether overexpression of Angptl6/AGF facilitates tissue repair processes in response to UV‐B irradiation. To test this hypothesis, we subjectedAngptl6/AGFtransgenic mice to acute or chronic UV‐B exposure. Surprisingly, transgenic mice showed enhanced photosensitivity to subthreshold doses of UV‐B that did not induce skin alterations in wild‐type littermates. Marked enlargement of blood vessels was observed after a single exposure to UV‐B inAngptl6/AGFtransgenic mice, although no epidermal changes were observed. Chronic UV‐B exposure over 14 weeks promoted cutaneous skin damage inAngptl6/AGFtransgenic mice, whereas wild‐type mice showed little or no macroscopic skin alteration. In addition to pronounced angiogenesis and epidermal hyperplasia, marked enlargement of dermal lymphatic vessels was observed in UV‐B‐exposedAngptl6/AGFtransgenic mice. Electron microscopy analysis further revealed that the number and size of collagen bundles in the dermis was markedly reduced after chronic UV‐B exposure inAngptl6/AGFtransgenic mice. Taken together, these results indicate that ectopic expression of Angptl6/AGF in mice likely promotes UV‐B‐induced skin alterations, and that angiogenesis could be a therapeutic target in prevention of skin photo‐aging.