The pro-inflammatory environment in recalcitrant diabetic foot wounds.
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.
Acosta
Jorge Berlanga
JB
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
del Barco
Diana Garcia
DG
Vera
Danay Cibrian
DC
Savigne
William
W
Lopez-Saura
Pedro
P
Guillen Nieto
Gerardo
G
Schultz
Gregory S
GS
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*
D051017:Apoptosis Regulatory Proteins; D017127:Glycation End Products, Advanced; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D020782:Matrix Metalloproteinases