title: A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production.
abstract: 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.
authors: 107 Laboratory, Departments of Nephrology and Endocrinology, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, Japan. noiri-tky@umin.ac.jp
authors: Kenjiro
authors: K
authors: Honda
authors: Koji
authors: K
authors: Okamoto
authors: Yasuhiro
authors: Y
authors: Mochida
authors: Kunihiro
authors: K
authors: Ishioka
authors: Machiko
authors: M
authors: Oka
authors: Kyoko
authors: K
authors: Maesato
authors: Ryota
authors: R
authors: Ikee
authors: Hidekazu
authors: H
authors: Moriya
authors: Sumi
authors: S
authors: Hidaka
authors: Takayasu
authors: T
authors: Ohtake
authors: Kent
authors: K
authors: Doi
authors: Toshiro
authors: T
authors: Fujita
authors: Shuzo
authors: S
authors: Kobayashi
authors: Eisei
authors: E
authors: Noiri
mesh_terms: D000368:Aged; D000818:Animals; D003646:Debridement / Q000379:methods*; D004175:Diptera; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007814:Larva; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008875:Middle Aged; D041681:NIH 3T3 Cells; D010447:Peptide Hydrolases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000502:physiology*
chemical_list: D017228:Hepatocyte Growth Factor; D010447:Peptide Hydrolases