Topical erythropoietin promotes wound repair in diabetic rats
Open accessAbstract
Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.
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Previous studies have demonstrated that platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor, or erythropoietin can improve healing in diabetic mice.
“Although previous studies have demonstrated that platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor (VEGF), or erythropoietin can improve healing in diabetic mice (13,36,37)”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [37]
Cites
1 retracted
Galeano, M., Altavilla, D., Bitto, A., et al. (2006) · Critical Care Medicine · doi:10.1097/01.ccm.0000206468.18653.ec · Cited by 151 · see citing works
RetractedCorrection of the Anemia of End-Stage Renal Disease with Recombinant Human Erythropoietin
Eschbach, J. W., Egrie, J. C., Downing, M. R., Browne, J. K., & Adamson, J. W. (1987) · New England Journal of Medicine · doi:10.1056/nejm198701083160203 · Cited by 1,987 · see citing works
Molecular Understanding of Hyperglycemia's Adverse Effects for Diabetic Complications
Sheetz, M. J. (2002) · JAMA · doi:10.1001/jama.288.20.2579 · Cited by 1,003 · see citing works
Diabetogenic action of streptozotocin: relationship of dose to metabolic response
Junod, A. F., Lambert, A. E., Stauffacher, W., & Renold, A. E. (1969) · Journal of Clinical Investigation · doi:10.1172/jci106180 · Cited by 931 · see citing works
Physiology and healing dynamics of chronic cutaneous wounds
Stadelmann, W. K., Digenis, A. G., & Tobin, G. R. (1998) · The American Journal of Surgery · doi:10.1016/s0002-9610(98)00183-4 · Cited by 910 · see citing works
Brown, L. F., Yeo, K. T., Berse, B., Yeo, T. K., Senger, D. R., Dvorak, H. F., & van de Water, L. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.5.1375 · Cited by 878 · see citing works
Cutaneous tissue repair: Basic biologic considerations. I
Clark, R. A. F. (1985) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(85)70213-7 · Cited by 582 · see citing works
Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells.
Anagnostou, A. A., Lee, E. S., Kessimian, N., et al. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.15.5978 · Cited by 578 · see citing works
Erythropoietin receptor mRNA expression in human endothelial cells.
Anagnostou, A. A., Liu, Z., Steiner, M. J., Chin, K., Lee, E. S., Kessimian, N., & Noguchi, C. T. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3974 · Cited by 564 · see citing works
Mustoe, T. A. (2004) · The American Journal of Surgery · doi:10.1016/s0002-9610(03)00306-4 · Cited by 437 · see citing works
Erythropoietin as an antiapoptotic, tissue-protective cytokine
Ghezzi, P., & Brines, M. (2004) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401450 · Cited by 327 · see citing works
Discovering erythropoietin's extra-hematopoietic functions: Biology and clinical promise
Brines, M., & Cerami, A. (2006) · Kidney International · doi:10.1038/sj.ki.5001546 · Cited by 290 · see citing works
Altavilla, D., Saitta, A., Cucinotta, D., Galeano, M., Deodato, B., Colonna, M. R., Torre, V., Russo, G. T., Sardella, A., Urna, G., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.3.667 · Cited by 273 · see citing works
Wen, T., Sadamoto, Y., Tanaka, J., et al. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10166 · Cited by 186 · see citing works
Healing of Diabetic Foot Ulcers and Pressure Ulcers With Human Skin Equivalent
Brem, H. (2000) · Archives of Surgery · doi:10.1001/archsurg.135.6.627 · Cited by 182 · see citing works
A Novel Role for Erythropoietin During Fibrin-Induced Wound-Healing Response
Haroon, Z. A., Amin, K., Jiang, X., et al. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63459-1 · Cited by 174 · see citing works
Hypoxic Induction of Prolyl 4-Hydroxylase α(I) in Cultured Cells
Takahashi, Y., Takahashi, S., Shiga, Y., Yoshimi, T., & Miura, T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14139 · Cited by 174 · see citing works
Galeano, M., Altavilla, D., Cucinotta, D., Russo, G. T., Calò, M., Bitto, A., Marini, H. R., Marini, R., Adamo, E. B., Seminara, P., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2509 · Cited by 173 · see citing works
Growth factors secreted by fibroblasts: role in healing diabetic foot ulcers
Mansbridge, J. N., Liu, K., Pinney, R. E., Patch, R., Ratcliffe, A., & Naughton, G. K. (1999) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.1999.00032.x · Cited by 164 · see citing works
Corral, C. J. (1999) · Archives of Surgery · doi:10.1001/archsurg.134.2.200 · Cited by 156 · see citing works
Treatment of nonhealing ulcers with allografts
Snyder, R. (2005) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2004.07.020 · Cited by 120 · see citing works
Li, F., Chong, Z. Z., & Maiese, K. (2004) · Neurosignals · doi:10.1159/000081963 · Cited by 113 · see citing works
RECOMBINANT HUMAN ERYTHROPOIETIN STIMULATES ANGIOGENESIS AND HEALING OF ISCHEMIC SKIN WOUNDS
Buemi, M., Galeano, M., Sturiale, A., Ientile, R., Crisafulli, C., Parisi, A., Catania, M. A., Calapai, G., Impal, P., Aloisi, C., et al. (2004) · Shock · doi:10.1097/01.shk.0000133591.47776.bd · Cited by 106 · see citing works
The EGF/ErbB Receptor Family and Apoptosis
Danielsen, A. J., & Maihle, N. J. (2002) · Growth Factors · doi:10.1080/08977190290022185 · Cited by 101 · see citing works
JELKMANN, W. E. B. (1994) · PubMed · Cited by 97 · see citing works
Shukla, A., Dubey, M., Srivastava, R., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8286 · Cited by 84 · see citing works
de Aguirre, Boya, P., Bellet, D. H., Faivre, S. J., Troalen, F., Bénard, J., Saulnier, P., Hopkins-Donaldson, S., Zangemeister‐Wittke, U., Kroemer, G., et al. (2004) · APOPTOSIS · doi:10.1023/b:appt.0000045781.46314.e2 · Cited by 78 · see citing works
Buemi, M., Vaccaro, M., Sturiale, A., et al. (2002) · Acta Dermato Venereologica · doi:10.1080/000155502762064520 · Cited by 77 · see citing works
Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin
Bodó, E., Kromminga, A., Funk, W., Laugsch, M., Duske, U., JELKMANN, W. E. B., & Paus, R. (2007) · The FASEB Journal · doi:10.1096/fj.07-8628com · Cited by 71 · see citing works
Effect of glycaemic control on apoptosis in diabetic wounds
Rai, N. K., Ansari, M., Kumar, M., et al. (2005) · Journal of Wound Care · doi:10.12968/jowc.2005.14.6.26792 · Cited by 61 · see citing works
The hypothesis of ‘biophysical matrix contraction’: wound contraction revisited
Farahani, R. M., & Kloth, L. C. (2008) · International Wound Journal · doi:10.1111/j.1742-481x.2007.00402.x · Cited by 56 · see citing works
Li, Z., Wang, Z. Z., Zheng, Y. Z., et al. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20436 · Cited by 49 · see citing works
Zhang, X., & Xu, B. (2000) · Anti-Cancer Drugs · doi:10.1097/00001813-200010000-00012 · Cited by 28 · see citing works
Tissue Adhesives in Wound Care.
Morgan, R. F. (1999) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-199911000-00057 · Cited by 26 · see citing works
Tissue Adhesives in Wound Care
Quinn, M. D., & James, V. (1998) · Cited by 25 · see citing works
The receptor for erythropoietin is present on cutaneous mast cells
Isogai, R., Takahashi, M., Aisu, K., et al. (2006) · Archives of Dermatological Research · doi:10.1007/s00403-005-0615-3 · Cited by 23 · see citing works
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Mirza, R. E., Fang, M. M., Weinheimer-Haus, E. M., Ennis, W. J., & Koh, T. J. (2014) · Diabetes · doi:10.2337/db13-0927 · Cited by 319 · see citing works
“Although previous studies have demonstrated that plateletderived growth factor, fibroblast growth factor, vascular endothelial growth factor (VEGF), or erythropoietin can improve healing in diabetic mice (13,36,37), our data indicate that targeting the inflammasome may provide a novel target for improving healing in d…”
Result
- Authors
- Hamed, S., Ullmann, Y., Masoud, M., Hellou, E., Khamaysi, Z., & Teot, L.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Hamed, Saher
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 130
- Issue
- 1
- Pages
- 287-294
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2000743316
- Cited by
- 102
- References
- 36
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 12 · 2020: 3 · 2019: 4 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Industry, Trade and Labor
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- erythropoietin, topical application, diabetic wound healing, chronic diabetic wounds, full-thickness skin wounds, wound closure, microvessel density, vascular endothelial growth factor, apoptosis, hydroxyproline
- MeSH terms
- Administration, Topical, Animals, Diabetes Mellitus, Experimental, Erythropoietin, Hydroxyproline, Male, Skin, Wound Healing, Wounds and Injuries, Rats, Sprague-Dawley, Apoptosis, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A, Rats
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