Molecular regulation of UVB-induced cutaneous angiogenesis

Molecular regulation of UVB-induced cutaneous angiogenesis
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DOI:
10.1046/j.1523-1747.1998.00378.x
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发表时间:
1998-11-01
影响因子:
6.5
通讯作者:
Fidler, IJ
Fidler, IJ
中科院分区:
医学1区
文献类型:
--
作者:
Bielenberg, DR;Bucana, CD;Fidler, IJ

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我们确定是否皮肤血管生成诱导小鼠暴露于紫外线-B(WB)辐射与正和负血管生成调节分子之间的不平衡。将未剃毛的C3 H/HeN小鼠暴露于单一剂量(15 kJ/m2)的UVB。在不同时间,处死小鼠,并对其外耳进行常规组织学和免疫组织化学处理。增殖细胞核抗原和溴脱氧尿苷抗体鉴定分裂细胞。抗CD 31/PECAM-1的抗体鉴定内皮细胞,抗碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子/血管通透性因子和干扰素-β(IFN-β)的抗体鉴定血管生成调节分子。WB照射后48 h表皮细胞增生明显,第7天达高峰,照射后24 h bFGF表达增加,72 h IFN-β表达下降,照射后血管内皮生长因子/血管通透性因子表达略有增加。bFGF和IFN-β之间的平衡改变与现有血管内内皮细胞增殖(溴脱氧尿苷+CD 31+细胞)增加相关,导致毛细血管扩张和新血管。UV诱导的表皮增生和皮肤血管生成在IFN-α/β受体敲除小鼠中最高。这些结果表明,在响应UVB辐射,分裂角质形成细胞产生阳性血管生成分子(bFGF),但不是一个负的血管生成分子(IFN-β),这种改变的平衡与增强皮肤血管生成。
We determined whether cutaneous angiogenesis induced by exposure of mice to ultraviolet-B (WB) radiation is associated with an imbalance between positive and negative angiogenesis-regulating molecules. Unshaved C3H/HeN mice were exposed to a single dose (15 kJ per m(2)) of UVB, At various times, the mice were killed, and their external ears were processed for routine histology and immunohistochemistry. Antibodies against proliferating cell nuclear antigen and bromodeoxyuridine identified dividing cells. Antibodies against CD31/PECAM-1 identified endothelial cells, and antibodies against basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor, and interferon-beta (IFN-beta) identified angiogenesis-regulating molecules. Epidermal hyperplasia was documented by 48 h and reached a maximum on day 7 after exposure to WB, The expression of bFGF increased by 24 h, whereas the expression of IFN-beta decreased by 72 h after exposure to WB, The expression of vascular endothelial growth factor/vascular permeability factor increased slightly after irradiation. The altered balance between bFGF and IFN-beta was associated with increased endothelial cell proliferation (bromodeoxyuridine + CD31 + cells) within existing blood vessels, leading to telangiectasia and new blood vessels. UV-induced epidermal hyperplasia and cutaneous angiogenesis were highest in IFN-alpha/beta receptor knockout mice. These results demonstrate that in response to UVB radiation, dividing keratinocytes produce a positive angiogenic molecule (bFGF) but not a negative angiogenic molecule (IFN-beta), and that this altered balance is associated with enhanced cutaneous angiogenesis.