Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds

• Published in: The Journal of surgical research Vol. 120; no. 1; pp. 47 - 55
• Main Authors: Ono, Ichiro, Yamashita, Toshiharu, Hida, Tokimasa, Jin, Hai-Ying, Ito, Yoshinori, Hamada, Hirobumi, Akasaka, Yoshikiyo, Ishii, Toshiharu, Jimbow, Kowichi
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2004; Elsevier
• Subjects: animal model; Animals; antiscar formation; Apoptosis - drug effects; Biological and medical sciences; breaking strength; Cicatrix - prevention & control; cytokine; Dermis - drug effects; fibroblast; General aspects; Genetic Therapy - methods; Growth Substances - administration & dosage; hepatocyte growth factor; Hepatocyte Growth Factor - genetics; incisional wound; Injections, Intradermal; Medical sciences; Models, Animal; Rats; Rats, Wistar; skin regeneration; tissue regeneration; wound healing; Wound Healing - drug effects; cytokine; tissue regeneration; wound healing; fibroblast; breaking strength; hepatocyte growth factor; incisional wound; antiscar formation; animal model; skin regeneration; Animal model; Hepatocyte growth factor; Acute; Cytokine; Wound; Medicine; Regeneration; Tissue; Local administration; Treatment; Gene; Surgery; Genetics; Skin; Derm; Cicatrization; Fibroblast; Strength
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2003.08.242

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 1 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.”