The combined effect of recombinant human epidermal growth factor and erythropoietin on full-thickness wound healing in diabetic rat model.

Joon Pio Hong, Sung Woo Park
Author Information
  1. Joon Pio Hong: Department of Plastic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non-healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non-healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague-Dawley rats were divided into three treatment groups (single treatment of rh-EPO or rh-EGF or combined treatment on a full-thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh-EPO and rh-EGF improved full-thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki-67 compared with single growth factor-treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor-treated groups (P < 0·05). This study demonstrated that the combined treatment of rh-EPO and rh-EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non-healing diabetic wounds.

Keywords

References

  1. Cancer. 2000 Dec 1;89(11):2258-65 [PMID: 11147596]
  2. Exp Biol Med (Maywood). 2003 Jan;228(1):1-14 [PMID: 12524467]
  3. J Biol Chem. 2004 May 14;279(20):20655-62 [PMID: 15020586]
  4. Int Rev Cytol. 1996;169:151-81 [PMID: 8843654]
  5. Arch Surg. 1993 Apr;128(4):423-9 [PMID: 7681277]
  6. Diabetes Metab Res Rev. 2008 May-Jun;24 Suppl 1:S25-30 [PMID: 18442179]
  7. Br J Surg. 2003 Feb;90(2):133-46 [PMID: 12555288]
  8. N Engl J Med. 1999 Sep 2;341(10):738-46 [PMID: 10471461]
  9. N Engl J Med. 1997 Mar 27;336(13):933-8 [PMID: 9070475]
  10. J Trauma. 1996 Jul;41(1):159-67 [PMID: 8676414]
  11. Development. 1998 Feb;125(4):725-32 [PMID: 9435292]
  12. J Exp Med. 1986 May 1;163(5):1319-24 [PMID: 3486247]
  13. Nature. 1997 Apr 17;386(6626):671-4 [PMID: 9109485]
  14. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11612-7 [PMID: 14500913]
  15. Int J Biochem Cell Biol. 1998 Nov;30(11):1169-74 [PMID: 9839443]
  16. Diabetes Care. 2003 Jun;26(6):1856-61 [PMID: 12766123]
  17. Plast Reconstr Surg. 1991 Aug;88(2):189-94; discussion 195-6 [PMID: 1852809]
  18. Nephrol Dial Transplant. 2006 Feb;21(2):330-6 [PMID: 16221709]
  19. Clin Investig. 1994;72(6 Suppl):S3-10 [PMID: 7950169]
  20. Nature. 2001 Aug 9;412(6847):641-7 [PMID: 11493922]
  21. J Invest Dermatol. 1990 May;94(5):624-9 [PMID: 2324518]
  22. Acta Derm Venereol. 2002;82(6):411-7 [PMID: 12575845]
  23. J Am Soc Nephrol. 1998 Nov;9(11):1998-2004 [PMID: 9808085]

MeSH Term

Animals
Bandages, Hydrocolloid
Diabetes Mellitus, Experimental
Drug Therapy, Combination
Epidermal Growth Factor
Erythropoietin
Follow-Up Studies
Humans
Rats
Rats, Sprague-Dawley
Recombinant Proteins
Skin
Treatment Outcome
Wound Healing
Wounds, Penetrating

Chemicals

Recombinant Proteins
Erythropoietin
Epidermal Growth Factor

Word Cloud

Created with Highcharts 10.0.0woundgrowthhealingtreatmentfactorcombinedsinglediabeticgroupsnon-healingcomparedrh-EPOrh-EGFfull-thicknesstimeprocessfactorsleadEpidermalErythropoietinstudytotalskinsizeimprovedP<0·05factor-treatedDiabeticchronicnormalinterruptedLackbloodsupplyinfectionlackfunctionalassumedconditionsenvironmentEGFactsprimarilystimulateepithelialcellacrossEPOhaematopoieticstimulatesproductiondifferentiationmaturationerythroidprecursorcellshypothesisedcombiningtwowillcompensatedeventuallyacceleration30Sprague-Dawleyratsdividedthreeassesseffectscomponentsmeasuredhistologyexaminedlightmicroscopyimmunohistochemicalanalysisproliferatingmarkersperformedsignificantlyaccelerating50%higherexpressionKi-67failedacceleratetreatmentsHoweversignificantimprovementfoundreductiongroupday4demonstratedpossiblysynergisticactionapplicationprovidesinsighttherapywoundseffectrecombinanthumanepidermalerythropoietinratmodelDiabetesWound

Similar Articles

Cited By (14)