Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers.
OBJECTIVE
To study the distribution of transforming growth factor-beta (TGF-beta) 1, 2 and 3, and TGF-beta receptor types I and II in diabetic foot ulcers, diabetic skin and normal skin by immunohistochemistry, immunofluorescence and Western blotting. We also compared the TGF-betas with those of chronic venous ulcers.


METHODS
Skin biopsies were obtained from the leg or the foot of non-diabetic and diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF-beta 1, 2 and 3 and TGF-beta receptors (RI and RII) was done by staining 8-microm skin sections using appropriate antibodies. Protein levels of TGF-beta were measured by Western blot analysis.


RESULTS
TGF-beta3 expression was increased in the epithelium at the edge of diabetic foot ulcers, being more intense than diabetic and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous ulcers compared with normal skin. However, TGF-beta1 expression was not increased in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic and normal skin. There was also no increase for the receptors in diabetic foot ulcers.


CONCLUSIONS
The lack of TGF-beta1 up-regulation in both diabetic foot ulcers and venous ulcers may explain the impaired healing in these chronic wounds, and could represent a general pattern for chronicity.
Jude
E B
EB
Department of Medicine and Diabetes, Manchester Royal Infirmary and School of Biological Sciences, University of Manchester, Manchester, UK. ejude@dc.cmht.nwest.nhs.uk
Blakytny
R
R
Bulmer
J
J
Boulton
A J M
AJ
Ferguson
M W J
MW
D030201:Activin Receptors, Type I / Q000032:analysis*; D015153:Blotting, Western; D017719:Diabetic Foot / Q000276:immunology / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology; D005260:Female; D016523:Foot Ulcer / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis*; D012016:Reference Values; D012867:Skin / Q000166:cytology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D014647:Varicose Ulcer / Q000473:pathology
D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II