Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation
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| Format: | Artículo científico |
| Language: | en |
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Medical Education Cooperation with Cuba
2020
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| _version_ | 1876460804404936704 |
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| author | Jorge Berlanga-Acosta |
| author_facet | Jorge Berlanga-Acosta |
| contents | Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation Jorge Berlanga-Acosta Hanlet Camacho-Rodríguez Yssel Mendoza-Marí Viviana Falcón-Cama Ariana García-Ojalvo Luis Herrera-Martínez Gerardo Guillén-Nieto Medicina Cuba ulcer diabetes amputation wound healing Lower-extremity diabetic ulcers are responsible for 80% of annual worldwide nontraumatic amputations. Epidermal growth factor (EGF) reduction is one of the molecular pillars of diabetic ulcer chronicity, thus EGF administration may be considered a type of replacement therapy. Topical EGF administration to improve and speed wound healing began in 1989 on burn patients as part of an acute-healing therapy. Further clinical studies based on topically administering EGF to different chronic wounds resulted in disappointing outcomes. An analysis of the literature on unsuccessful clinical trials identified a lack of knowledge concerning: (I) molecular and cellular foundations of wound chronicity and (II) the pharmacodynamic requisites governing EGF interaction with its receptor to promote cell response. Yet, EGF intra- and perilesional infiltration were shown to circumvent the pharmacodynamic limitations of topical application. Since the first studies, the following decades of basic and clinical research on EGF therapy for problem wounds have shed light on potential uses of growth factors in regenerative medicine. EGF’s molecular and biochemical effects at both local and systemic levels are diverse: (1) downregulation of genes encoding inflammation mediators and increased expression of genes involved in cell proliferation, angiogenesis and matrix secretion; (2) EGF intervention positively impacts both mesenchymal and epithelial cells, reducing inflammation and stimulating the recruitment of precursor circulating cells that promote the formation of new blood vessels; (3) at the subcellular level, upregulation of the EGF receptor with subsequent intracellular trafficking, including mitochondrial allocation along with restored morphology of multiple organelles; and (4) local EGF infiltration resulting in a systemic, organismal repercussion, thus contributing to attenuation of circulating inflammatory and catabolic reactants, restored reduction-oxidation balance, and decreased toxic glycation products and soluble apoptogenic effectors. It is likely that EGF treatment may rearrange critical epigenetic drivers of diabetic metabolic memory. 2020 artículo científico 1555-7960 https://www.redalyc.org/articulo.oa?id=437567141007 https://www.redalyc.org/journal/4375/437567141007/ https://www.redalyc.org/journal/4375/437567141007/html/ https://www.redalyc.org/journal/4375/437567141007/437567141007.epub https://www.redalyc.org/journal/4375/437567141007/movil https://doi.org/10.37757/MR2020.V22.N3.7 en http://www.redalyc.org/revista.oa?id=4375 MEDICC Review application/pdf Medical Education Cooperation with Cuba MEDICC Review (Estados Unidos de América) Num.3 Vol.22 |
| format | Artículo científico |
| id | redalyc_437567141007 |
| institution | Redalyc |
| language | en |
| publishDate | 2020 |
| publisher | Medical Education Cooperation with Cuba |
| spellingShingle | Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation Jorge Berlanga-Acosta Medicina Cuba ulcer diabetes amputation wound healing Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation Jorge Berlanga-Acosta Hanlet Camacho-Rodríguez Yssel Mendoza-Marí Viviana Falcón-Cama Ariana García-Ojalvo Luis Herrera-Martínez Gerardo Guillén-Nieto Medicina Cuba ulcer diabetes amputation wound healing Lower-extremity diabetic ulcers are responsible for 80% of annual worldwide nontraumatic amputations. Epidermal growth factor (EGF) reduction is one of the molecular pillars of diabetic ulcer chronicity, thus EGF administration may be considered a type of replacement therapy. Topical EGF administration to improve and speed wound healing began in 1989 on burn patients as part of an acute-healing therapy. Further clinical studies based on topically administering EGF to different chronic wounds resulted in disappointing outcomes. An analysis of the literature on unsuccessful clinical trials identified a lack of knowledge concerning: (I) molecular and cellular foundations of wound chronicity and (II) the pharmacodynamic requisites governing EGF interaction with its receptor to promote cell response. Yet, EGF intra- and perilesional infiltration were shown to circumvent the pharmacodynamic limitations of topical application. Since the first studies, the following decades of basic and clinical research on EGF therapy for problem wounds have shed light on potential uses of growth factors in regenerative medicine. EGF’s molecular and biochemical effects at both local and systemic levels are diverse: (1) downregulation of genes encoding inflammation mediators and increased expression of genes involved in cell proliferation, angiogenesis and matrix secretion; (2) EGF intervention positively impacts both mesenchymal and epithelial cells, reducing inflammation and stimulating the recruitment of precursor circulating cells that promote the formation of new blood vessels; (3) at the subcellular level, upregulation of the EGF receptor with subsequent intracellular trafficking, including mitochondrial allocation along with restored morphology of multiple organelles; and (4) local EGF infiltration resulting in a systemic, organismal repercussion, thus contributing to attenuation of circulating inflammatory and catabolic reactants, restored reduction-oxidation balance, and decreased toxic glycation products and soluble apoptogenic effectors. It is likely that EGF treatment may rearrange critical epigenetic drivers of diabetic metabolic memory. 2020 artículo científico 1555-7960 https://www.redalyc.org/articulo.oa?id=437567141007 https://www.redalyc.org/journal/4375/437567141007/ https://www.redalyc.org/journal/4375/437567141007/html/ https://www.redalyc.org/journal/4375/437567141007/437567141007.epub https://www.redalyc.org/journal/4375/437567141007/movil https://doi.org/10.37757/MR2020.V22.N3.7 en http://www.redalyc.org/revista.oa?id=4375 MEDICC Review application/pdf Medical Education Cooperation with Cuba MEDICC Review (Estados Unidos de América) Num.3 Vol.22 |
| title | Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation |
| topic | Medicina Cuba ulcer diabetes amputation wound healing |
| url | https://www.redalyc.org/articulo.oa?id=437567141007 https://www.redalyc.org/journal/4375/437567141007/ https://www.redalyc.org/journal/4375/437567141007/html/ https://www.redalyc.org/journal/4375/437567141007/437567141007.epub https://www.redalyc.org/journal/4375/437567141007/movil https://doi.org/10.37757/MR2020.V22.N3.7 |