Recombinant hepatocyte growth factor accelerates cutaneous wound healing in a diabetic mouse model.
We examined effects of recombinant hepatocyte growth factor (HGF) on cutaneous wound healing, using a full-thickness cutaneous excision model in diabetic mice. Topical administration of HGF, as well as basic fibroblast growth factor (bFGF), promoted the rate of wound closure and re-epithelialization. Both HGF and bFGF enhanced expansion of the granulation tissue and stimulated neovascularization on day 7 postwounding, wherein the increase in microvessel density in HGF-treated wounds was higher than that in bFGF-treated wounds. Matrix metalloproteinases (MMP-2 and MMP-9) activities involved in cell migration, angiogenesis, and extracellular matrix (ECM) remodeling, were enhanced by HGF-treatment on day 7. On day 28 postwounding (later stages of wound healing), granulation tissue in bFGF-treated wounds remained to a greater extent than that seen in saline- and HGF-treated wounds. Likewise, bFGF- but not HGF-treatment stimulated DNA synthesis of fibroblasts in granulation tissue, suggesting that HGF stimulates wound healing with lesser degree of susceptibility to cutaneous scarring. We propose that supplement of HGF may be a potential therapeutic approach for treatment of cutaneous ulcer.
Yoshida
Saho
S
Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Yamadaoka 2-2-B7, Suita 565-0871, Osaka, Japan.
Matsumoto
Kunio
K
Tomioka
Daisaku
D
Bessho
Kazuhiko
K
Itami
Satoshi
S
Yoshikawa
Kunihiko
K
Nakamura
Toshikazu
T
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005780:Gelatin / Q000494:pharmacology; D018093:Gelatinases / Q000378:metabolism; D017353:Gene Deletion; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000737:chemistry*; D013997:Time Factors; D014945:Wound Healing
D018076:DNA, Complementary; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D005780:Gelatin; D004247:DNA; D018093:Gelatinases; D001973:Bromodeoxyuridine