Berlanga-Acosta Jorge, Camacho-Rodríguez Hanlet, Mendoza-Marí Yssel, Falcón-Cama Viviana, García-Ojalvo Ariana, Herrera-Martínez Luis, Guillén-Nieto Gerardo
MEDICC Rev. 2020 Jul;22(3):24-31. doi: 10.37757/MR2020.V22.N3.7.
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 ad-ministration 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 out-comes. An analysis of the literature on unsuccessful clinical trials identifi ed a lack of knowledge concerning: (I) molecular and cellular foundations of wound chronicity and (II) the phar-macodynamic requisites governing EGF interaction with its receptor to promote cell response. Yet, EGF intra- and perile-sional infi ltration were shown to circumvent the pharmacody-namic limitations of topical application. Since the fi rst 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 infl ammation mediators and increased expression of genes involved in cell proliferation, angiogenesis and matrix secretion; (2) EGF in-tervention positively impacts both mesenchymal and epithelial cells, reducing infl ammation 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 traffi cking, includ-ing mitochondrial allocation along with restored morphology of multiple organelles; and (4) local EGF infi ltration resulting in a systemic, organismal repercussion, thus contributing to attenuation of circulating infl ammatory and catabolic reac-tants, 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. KEYWORDS Epidermal Growth Factor, diabetes, diabetes complications, wound healing, diabetic foot, amputation, ulcer, Cuba.
下肢糖尿病溃疡占全球每年非创伤性截肢的80%。表皮生长因子（EGF）减少是糖尿病溃疡慢性化的分子支柱之一，因此给予EGF可被视为一种替代疗法。1989年开始对烧伤患者进行局部给予EGF以改善和加速伤口愈合，作为急性愈合治疗的一部分。基于对不同慢性伤口局部给予EGF的进一步临床研究结果令人失望。对不成功的临床试验文献分析发现，缺乏关于：（I）伤口慢性化的分子和细胞基础，以及（II）控制EGF与其受体相互作用以促进细胞反应的药效学要求的知识。然而，EGF病灶内和病灶周围浸润已显示可规避局部应用的药效学限制。自最初的研究以来，随后几十年关于EGF治疗疑难伤口的基础和临床研究揭示了生长因子在再生医学中的潜在用途。EGF在局部和全身水平的分子和生化作用是多样的：（1）编码炎症介质的基因下调，以及参与细胞增殖、血管生成和基质分泌的基因表达增加；（2）EGF干预对间充质细胞和上皮细胞均有积极影响，减少炎症并刺激促进新血管形成的循环前体细胞募集；（3）在亚细胞水平，EGF受体上调并随后进行细胞内运输，包括线粒体分配以及多个细胞器形态的恢复；（4）局部EGF浸润导致全身、机体反应，从而有助于减轻循环中的炎症和分解代谢反应物，恢复氧化还原平衡，并减少有毒糖基化产物和可溶性凋亡效应物。EGF治疗可能会重新排列糖尿病代谢记忆的关键表观遗传驱动因素。关键词表皮生长因子、糖尿病、糖尿病并发症、伤口愈合、糖尿病足、截肢、溃疡、古巴
