Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds
Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds
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DOI：
10.1016/j.jss.2003.08.242
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发表时间：
2004-07-01
影响因子：
2.2
通讯作者：
Jimbow, K
中科院分区：
文献类型：
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作者：
Ono, I;Yamashita, T;Jimbow, K
肝细胞生长因子（HGF）具有多种生物活性，如有丝分裂、促运动抗凋亡、抗纤维和形态形成。它对内皮细胞也有血管生成和血管保护作用。本研究的目的是通过将HGF基因局部施用于大鼠背部的急性切口皮肤伤口，来表征HGF在伤口愈合中的作用。为了制造伤口，在Wistar大鼠的背部剪下3个2厘米长的切口。伤口深及筋膜。伤口含有肉赘肉，每隔2厘米创面。缝合后，皮下注射HGF基因。采用TUNEL法和免疫检测活性caspase-3检测创面病变中的凋亡细胞。在hgf处理的动物中，我们发现细胞凋亡几乎完全被抑制，伤口愈合组织良好。组织病理学检查显示，与对照组相比，hgf治疗动物的成纤维细胞增殖受到抑制，疤痕形成不太明显。据认为，术后立即给予HGF基因可能通过抑制细胞凋亡来促进愈合过程，这种情况发生在缝合切口后1周的对照组中。此外，将HGF基因引入伤口周围细胞，局部HGF表达增加，可能是通过促进真皮组织再生，从而减少疤痕，这是由于其抗纤维化作用。因此，通过基因治疗补充HGF可能是治疗伤口的有效策略，因为它可以增加真皮层的再生，从而实现“无疤痕伤口愈合”。(C) 2004爱思唯尔公司版权所有。
Hepatocyte growth factor (HGF) has a number of biological activities, e.g., mitogenic, motogenic antiapoptotic, antifibrous, and morphogenic. It also has angiogenic and angioprotective activities for endothelial cells. The aim of this study was to characterize the role of HGF in wound healing by administering the HGF gene locally to acute incisional skin wounds created on the backs of rats. To create wounds, the backs of Wistar rats were clipped and three 2-cm-long incisional. wounds were made deep to the fascia. The wounds contained pannicrus carnosum and were created at intervals of 2 cm. After suturing, the HGF gene was then administered intradermally. Apoptotic cells in wound lesions were identified by TUNEL method as well as by immunological detection of active caspase-3. In the HGF-treated animals, we found almost complete suppression of apoptosis and well-organized wound healing. Histopathological examination revealed that the proliferation of fibroblasts was suppressed and that scar formation was less apparent in the HGF-treated animals compared to the controls. It is thought that administration of the HGF gene immediately after surgery may enhance the healing process through suppressing apoptosis, which occurred in the controls I week after suturing the incisional wound. In addition, locally increased HGF expression due to the introduction of the HGF gene to cells around wounds enhances dermal regeneration, possibly by promoting regeneration of dermal tissue, which results in less scarring due to its antifibrotic effect. Thus, HGF supplementation through gene therapy may be an effective strategy for treating wounds, as it increases the regeneration of the dermis to allow for "scarless wound healing." (C) 2004 Elsevier Inc. All rights reserved.