Hepatocyte growth factor; expression, concentration and biological activity in chronic leg ulcers.
BACKGROUND
Hepatocyte growth factor (HGF) is a multifunctional cytokine that is involved in recovery process after organ injuries.


OBJECTIVE
We studied HGF and the membrane bound receptor, c-met locally in patients who suffered from chronic leg ulcers (> or =1 year) caused by venous insufficiency.


METHODS
Skin biopsies from the edge of the ulcers were taken from patients (n=13) and studied by immunohistochemical staining for detection of HGF and c-met. Skin biopsies from healthy volunteers (n=10) were used as the control material. Ulcer secretion from chronic ulcers (n=11) was examined for the presence of HGF by ELISA and the concentration of HGF was compared with acute ulcers in healthy controls (n=10) and in patients operated for a non-invasive breast cancer (n=12).


RESULTS
We observed that c-met expression in the ulcer area increased significantly in chronic ulcers compared to controls (p=0.005). Concentration of ulcer-HGF in the patients with chronic ulcer was significantly higher than acute ulcers (p<0.01). The biological activity of HGF in ulcer secret was assessed in-vitro in transferred, mouse skin epithelial cell monolayer. Enhanced migration and morphologic changes were seen after adding ulcer secret from acute ulcers (> 1 ng/mL) that was inhibited by anti-HGF antibodies. No biological activity was observed by adding ulcer secret from chronic ulcers irrespective HGF concentration.


CONCLUSIONS
We conclude that in chronic skin ulcers decreased biological activity of endogenous HGF and overexpression of c-met is seen which might explain fibrosis and delayed recovery. Administration of exogenous active HGF might contribute to accelerated healing in these patients.
Nayeri
Fariba
F
Division of Infectious Diseases, Faculty of Health Science, University Hospital, S-58185 Linköping, Sweden. fariba.nayeri@lio.se
Olsson
Hans
H
Peterson
Curt
C
Sundqvist
Tommy
T
D000328:Adult; D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007871:Leg Ulcer / Q000378:metabolism*; D008297:Male; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D012867:Skin / Q000473:pathology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014456:Ulcer / Q000378:metabolism; D014689:Venous Insufficiency / Q000473:pathology; D014945:Wound Healing
D016207:Cytokines; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met