Maggot debridement therapy (MDT) is effective for treating intractable
wounds, but its precise molecular mechanism, including the association between MDT and
growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable
wounds of lower extremities because they did not respond to conventional
therapies. Significant increases of
hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT (P < 0.05), but no significant change was found for
vascular endothelial growth factor (
VEGF),
basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or
tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and
protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group (P < 0.01). Furthermore,
protease inhibitors suppressed the increase of HGF (P < 0.05). The HGF expression was increased in proportion to the ES
protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than
chymotrypsin or
bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing
therapy.