Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing.

Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing.
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DOI:
10.1084/jem.176.5.1375
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发表时间:
1992-11-01
影响因子:
15.3
通讯作者:
VANDEWATER, L
VANDEWATER, L
中科院分区:
医学1区
文献类型:
--
作者:
BROWN, LF;YEO, KT;BERSE, B;YEO, TK;SENGER, DR;DVORAK, HF;VANDEWATER, L

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即使在损伤停止后,持续的微血管对血浆蛋白的高渗透性也是正常伤口愈合的特征,但对其了解甚少。它导致纤维蛋白原外渗,纤维蛋白原凝结形成纤维蛋白,纤维蛋白充当临时基质并促进血管生成和瘢痕形成。我们目前的证据表明,血管通透性因子(VPF,也称为血管内皮生长因子)可能是负责的高渗透性状态,以及血管生成,愈合伤口的特征。在愈合的豚鼠和大鼠断层穿刺活检皮肤伤口中,通过其外渗循环大分子示踪剂(胶体碳,荧光葡聚糖)的能力,确定了高渗透性血管。血管通透性在2-3 d达到最大,但持续到伤后7 d。最初在伤口边缘发现渗漏血管,后来在表皮下肉芽组织中发现渗漏血管,因为角质形成细胞迁移覆盖裸露的伤口表面。在这7天的时间间隔内,血管生成也很突出。原位杂交显示,大量增加的VPF mRNA表达的角质形成细胞,最初那些在伤口边缘,并在以后的时间间隔,角质形成细胞迁移到覆盖伤口表面,偶尔单核细胞也表达VPF mRNA。用免疫荧光法检测培养的人角质形成细胞分泌的VPF。这些数据确定角质形成细胞作为VPF基因转录物和蛋白质的重要来源,将VPF表达与持续的血管通透性过高和血管生成相关,并表明VPF是伤口愈合中的重要细胞因子。
Persistent microvascular hyperpermeability to plasma proteins even after the cessation of injury is a characteristic but poorly understood feature of normal wound healing. It results in extravasation of fibrinogen that clots to form fibrin, which serves as a provisional matrix and promotes angiogenesis and scar formation. We present evidence indicating that vascular permeability factor (VPF; also known as vascular endothelial growth factor) may be responsible for the hyperpermeable state, as well as the angiogenesis, that are characteristic of healing wounds. Hyperpermeable blood vessels were identified in healing split-thickness guinea pig and rat punch biopsy skin wounds by their capacity to extravasate circulating macromolecular tracers (colloidal carbon, fluoresceinated dextran). Vascular permeability was maximal at 2-3 d, but persisted as late as 7 d after wounding. Leaky vessels were found initially at the wound edges and later in the subepidermal granulation tissue as keratinocytes migrated to cover the denuded wound surface. Angiogenesis was also prominent within this 7-d interval. In situ hybridization revealed that greatly increased amounts of VPF mRNA were expressed by keratinocytes, initially those at the wound edge, and, at later intervals, keratinocytes that migrated to cover the wound surface; occasional mononuclear cells also expressed VPF mRNA. Secreted VPF was detected by immunofluoroassay of medium from cultured human keratinocytes. These data identify keratinocytes as an important source of VPF gene transcript and protein, correlate VPF expression with persistent vascular hyperpermeability and angiogenesis, and suggest that VPF is an important cytokine in wound healing.
DOI: 10.1091/mbc.3.2.211
发表时间: 1992-02-01
影响因子: 3.3
作者:
BERSE, B;BROWN, LF;SENGER, DR
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发表时间: 1992-01-01
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发表时间: 1989-08
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