Intradermal injection of transforming growth factor-beta1 gene enhances wound healing in genetically diabetic mice.
OBJECTIVE
To evaluate the biologic effect of direct cutaneous TGF-beta1 gene delivery on impaired wound healing models using genetically diabetic mice.


METHODS
Diabetic mice (C57BKS.Cg-m +/+ Leprdb female mice) with 1 cm x 1 cm excisional wounds were intradermally injected with 60 microg of plasmid DNA encoding TGF-beta1 gene. The wound closure was measured up to 14 days postwounding. At days 7 and 14 postwounding, sections of skin were taken for hematoxylin and eosin and Masson's trichome staining to examine the morphology and collagen deposition. The cell proliferation and TGF-beta1 gene expression were studied using immunohistochemical stainings for 5-bromo-2-deoxyuridine and for TGF-beta1.


RESULTS
A higher cell proliferation rate and a denser and more organized new extracellular matrix were observed in the treated wound site. Complete wound closure was detected as early as 7 days for TGF-beta1-treated group in comparison with 11-14 days for the untreated, control plasmid DNA- and PBS-treated groups.


CONCLUSIONS
A single intradermal injection of TGF-beta1 plasmid DNA was sufficient to enhance wound healing. This approach represents a new strategy that may be applied to the treatment of excisional wounds in human diabetic patients.
Chesnoy
Sophie
S
Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Lee
Pui-Yan
PY
Huang
Leaf
L
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007271:Injections, Intradermal; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects*
D011994:Recombinant Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004247:DNA