PDGF and TGF-α Act Synergistically to Improve Wound Healing in the Genetically Diabetic Mouse

Rebeccah L. Brown, Matthew P. Breeden, David G Greenhalgh

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Impaired wound healing results in significant morbidity for the surgical patient. The genetically diabetic (C57BL/KsJ-db/db) mouse is obese, hyperglycemic, insulin-resistant, and exhibits markedly impaired wound healing. Previous studies have demonstrated that the fibroblast mitogens, BB homodimer of platelet-derived growth factor (PDGF-BB) or basic fibroblast growth factor, plus insulin-like growth factor, act synergistically to enhance wound closure in the genetically diabetic mouse. The purpose of this study was to determine whether the keratinocyte mitogens, epidermal growth factor (EGF) or transforming growth factor-α (TGF-α), in combination with the fibroblast mitogen, PDGF-BB, would produce a similar synergistic enhancement in tissue repair. Full-thickness skin wounds created on the backs of diabetic mice received topical applications of vehicle (5% polyethylene glycol), PDGF-BB (10 μg), EGF (1 μg), TGF-α (1 μg), or the combination of PDGF (10 μg) and EGF (1 μg) or TGF-α (1 μg) for 5 consecutive days starting at wounding. Application of PDGF-BB or TGF-α alone to wounds in diabetic animals improved wound closure when compared to vehicle treatment. EGF did not affect healing and did not have any additive effects when combined with PDGF-BB. Significant improvements in wound closure were observed with the combination of PDGF-BB and TGF-α when compared to treatment with the individual growth factors. The PDGF-BB/TGF-α combination accelerated healing in the diabetic animals to a rate that was closer to that seen in nondiabetic mice. By histologic analysis at Day 15, all criteria for healing were more advanced in the PDGF-BB/TGF-α combination wounds when compared to the other treatment groups. As all wounds approached complete healing by Day 21, these differences were lost. In summary, PDGF-BB and TGF-α acted synergistically in genetically diabetic mice to promote early wound healing beyond that of the individual growth factors. Similar synergy was not observed with the combination of PDGF-BB and EGF.

Original languageEnglish (US)
Pages (from-to)562-570
Number of pages9
JournalJournal of Surgical Research
Volume56
Issue number6
DOIs
StatePublished - Jun 1994
Externally publishedYes

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Transforming Growth Factors
Wound Healing
Epidermal Growth Factor
Wounds and Injuries
Mitogens
Intercellular Signaling Peptides and Proteins
platelet-derived growth factor BB
Fibroblasts
Obese Mice
Somatomedins
Fibroblast Growth Factor 2
Keratinocytes
Insulin
Morbidity
Skin

ASJC Scopus subject areas

  • Surgery

Cite this

PDGF and TGF-α Act Synergistically to Improve Wound Healing in the Genetically Diabetic Mouse. / Brown, Rebeccah L.; Breeden, Matthew P.; Greenhalgh, David G.

In: Journal of Surgical Research, Vol. 56, No. 6, 06.1994, p. 562-570.

Research output: Contribution to journalArticle

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abstract = "Impaired wound healing results in significant morbidity for the surgical patient. The genetically diabetic (C57BL/KsJ-db/db) mouse is obese, hyperglycemic, insulin-resistant, and exhibits markedly impaired wound healing. Previous studies have demonstrated that the fibroblast mitogens, BB homodimer of platelet-derived growth factor (PDGF-BB) or basic fibroblast growth factor, plus insulin-like growth factor, act synergistically to enhance wound closure in the genetically diabetic mouse. The purpose of this study was to determine whether the keratinocyte mitogens, epidermal growth factor (EGF) or transforming growth factor-α (TGF-α), in combination with the fibroblast mitogen, PDGF-BB, would produce a similar synergistic enhancement in tissue repair. Full-thickness skin wounds created on the backs of diabetic mice received topical applications of vehicle (5{\%} polyethylene glycol), PDGF-BB (10 μg), EGF (1 μg), TGF-α (1 μg), or the combination of PDGF (10 μg) and EGF (1 μg) or TGF-α (1 μg) for 5 consecutive days starting at wounding. Application of PDGF-BB or TGF-α alone to wounds in diabetic animals improved wound closure when compared to vehicle treatment. EGF did not affect healing and did not have any additive effects when combined with PDGF-BB. Significant improvements in wound closure were observed with the combination of PDGF-BB and TGF-α when compared to treatment with the individual growth factors. The PDGF-BB/TGF-α combination accelerated healing in the diabetic animals to a rate that was closer to that seen in nondiabetic mice. By histologic analysis at Day 15, all criteria for healing were more advanced in the PDGF-BB/TGF-α combination wounds when compared to the other treatment groups. As all wounds approached complete healing by Day 21, these differences were lost. In summary, PDGF-BB and TGF-α acted synergistically in genetically diabetic mice to promote early wound healing beyond that of the individual growth factors. Similar synergy was not observed with the combination of PDGF-BB and EGF.",
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