Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds.
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."
Ono
Ichiro
I
Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan. ichiro@sapmed.ac.jp
Yamashita
Toshiharu
T
Hida
Tokimasa
T
Jin
Hai-Ying
HY
Ito
Yoshinori
Y
Hamada
Hirobumi
H
Akasaka
Yoshikiyo
Y
Ishii
Toshiharu
T
Jimbow
Kowichi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002921:Cicatrix / Q000517:prevention & control; D020405:Dermis / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods*; D006133:Growth Substances / Q000008:administration & dosage*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D007271:Injections, Intradermal; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D006133:Growth Substances; D017228:Hepatocyte Growth Factor