title: The pro-inflammatory environment in recalcitrant diabetic foot wounds.
abstract: Lower extremity ulceration is one of the serious and long-term diabetic complications rendering a significant social burden in terms of amputation and quality-of-life reduction. Diabetic patients experience a substantial wound-healing deficit. These lesions are featured by an exaggerated and prolonged inflammatory reaction with a significant impairment in local bacterial invasion control. Experimental and clinical evidences document the deleterious consequences of the wound's pro-inflammatory phenotype for the repair process. From a biochemical standpoint, hyperinflammation favours wound matrix degradation, thus, amplifying a pre-existing granulation tissue productive cells' invasiveness and recruitment deficit. Tumour necrosis factor perpetuates homing of inflammatory cells, triggers pro-apoptotic genes and impairs reepithelialisation. Advanced glycation end-products act in concert with inflammatory mediators and commit fibroblasts and vascular cells to apoptosis, contributing to granulation tissue demise. Therapeutic approaches aimed to downregulate hyperinflammation and/or attenuate glucolipotoxicity may assist in diabetic wound healing by dismantling downstream effectors. These medical interventions are demanded to reduce amputations in an expanding diabetic population.
authors.affiliation: Biomedical Research Direction, Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Avenida 31 e/158 y 190, Playa, PO Box 6162, Havana 10600, Cuba. jorge.berlanga@cigb.edu.cu
authors.forename: Jorge Berlanga
authors.initials: JB
authors.lastname: Acosta
authors.forename: Diana Garcia
authors.initials: DG
authors.lastname: del Barco
authors.forename: Danay Cibrian
authors.initials: DC
authors.lastname: Vera
authors.forename: William
authors.initials: W
authors.lastname: Savigne
authors.forename: Pedro
authors.initials: P
authors.lastname: Lopez-Saura
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillen Nieto
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Schultz
mesh_terms: D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D017719:Diabetic Foot / Q000276:immunology* / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000276:immunology*; D006097:Granulation Tissue / Q000276:immunology; D006801:Humans; D007249:Inflammation; D020782:Matrix Metalloproteinases / Q000276:immunology*; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000276:immunology*; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D017127:Glycation End Products, Advanced; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D020782:Matrix Metalloproteinases