Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration

Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration
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DOI:
10.1073/pnas.1531901100
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发表时间:
2003-08-05
影响因子:
11.1
通讯作者:
Suda, T
Suda, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Oike, Y;Yasunaga, K;Suda, T

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我们在此报告了一种血管生成素相关生长因子(AGF)的鉴定。为了检测AGF在体内的生物学功能,我们建立了在表皮角质形成细胞中表达AGF的转基因小鼠(K14-AGF)。K14-AGF小鼠表现出耳朵、鼻子和眼皮肿胀和红肿。对K14-AGF小鼠的组织学分析显示,与非转基因对照相比,K14-AGF小鼠的表皮显着增厚,皮肤中增殖的表皮细胞和血管细胞显着增加。此外,我们发现在愈合过程中伤口迅速闭合,K14-AGF小鼠耳朵上穿孔的异常闭合。此外,我们观察到AGF在血小板和肥大细胞中表达,并在创伤皮肤中检测到,而在正常皮肤组织中未检测到AGF的表达,这表明这些浸润性细胞来源的AGF影响表皮的增殖,从而在伤口愈合过程中发挥作用。这些发现表明,表皮角质形成细胞中AGF的生物学功能可能导致创面护理和表皮再生医学的新治疗策略。
We report here the identification of an angiopoietin-related growth factor (AGF). To examine the biological function of AGF in vivo, we created transgenic mice expressing AGF in epidermal keratinocytes (K14-AGF). K14-AGF mice exhibited swollen and reddish ears, nose and eyelids. Histological analyses of K14-AGF mice revealed significantly thickened epidermis and a marked increase in proliferating epidermal cells as well as vascular cells in the skin compared with nontransgenic controls. In addition, we found rapid wound closure in the healing process and an unusual closure of holes punched in the ears of K14-AGF mice. Furthermore, we observed that AGF is expressed in platelets and mast cells, and detected at wounded skin, whereas there was no expression of AGF detected in normal skin tissues, suggesting that AGF derived from these infiltrated cells affects epidermal proliferation and thereby plays a role in the wound healing process. These findings demonstrate that biological functions of AGF in epidermal keratinocytes could lead to novel therapeutic strategies for wound care and epidermal regenerative medicine.