Recombinant Hepatocyte Growth Factor Accelerates Cutaneous Wound Healing in a Diabetic Mouse Model

Abstract

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.

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

“…31 Moreover, HGF stimulates wound healing, with less susceptibility to cutaneous scarring. 32 In this study, re-epithelialization and microvasculation of the wound were promoted after HGF gene transfer. We measured the expression of human HGF protein in the skin around the wound.…”

Transforming Growth Factor-β Signaling in Prostate Stromal Cells Supports Prostate Carcinoma Growth by Up-regulating Stromal Genes Related to Tissue Remodeling

“…Under a physiologic wound healing process, these TGFh actions are balanced with that of HGF. Gene transfer of HGF has been shown to accelerate cutaneous wound healing with a concurrent decrease of TGFh1 compared with control wounds (47). Conversely, inhibition of HGF signaling has been shown to retard cutaneous wound healing (48).…”

Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery

“…2 and 3) have been shown to be important for diabetic wound healing. 15,16,[38][39][40][41][42] It is, therefore, reasonable to hypothesize that the observed increase in the production of these proteins plays at least a partial role in the increased rate of diabetic wound healing associated with ASC MA treatment. The synergistic interactions between growth factors and ECM proteins (in particular those involving growth factors and ECM components upregulated in MAs like insulin-like growth factor binding protein-1, transforming growth factor-b1, vascular endothelial growth factor, hepatocyte growth factor, decorin, biglycan, and fibronectin) are increasingly being recognized as playing a significant role in wound healing and tissue repair, 13,21,[43][44][45][46][47][48][49][50] and although the secreted protein values reported in this paper do not reflect the full effect of the synergy and sequestration of secreted proteins (proteins sequestered by ECM are not interrogated by ELISA techniques), it is probable that such signaling plays a role in the enhanced in vivo activity of ASCs formulated as MAs relative to ASC suspensions.…”