RGD Reference Report - Mechanisms involved in the development and healing of diabetic foot ulceration. - Rat Genome Database

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Mechanisms involved in the development and healing of diabetic foot ulceration.

Authors: Dinh, T  Tecilazich, F  Kafanas, A  Doupis, J  Gnardellis, C  Leal, E  Tellechea, A  Pradhan, L  Lyons, TE  Giurini, JM  Veves, A 
Citation: Dinh T, etal., Diabetes. 2012 Nov;61(11):2937-47. doi: 10.2337/db12-0227. Epub 2012 Jun 11.
RGD ID: 8547813
Pubmed: PMID:22688339   (View Abstract at PubMed)
PMCID: PMC3478547   (View Article at PubMed Central)
DOI: DOI:10.2337/db12-0227   (Journal Full-text)

We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 +/- 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-alpha, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTPN1Humandiabetes mellitus  IEP protein:increased expression:skin of forearm (human)RGD 
Ptpn1Ratdiabetes mellitus  ISOPTPN1 (Homo sapiens)protein:increased expression:skin of forearm (human)RGD 
Ptpn1Mousediabetes mellitus  ISOPTPN1 (Homo sapiens)protein:increased expression:skin of forearm (human)RGD 
MMP9HumanDiabetic Foot severityIEP  RGD 
Mmp9RatDiabetic Foot severityISOMMP9 (Homo sapiens) RGD 
Mmp9MouseDiabetic Foot severityISOMMP9 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)
Ptpn1  (protein tyrosine phosphatase, non-receptor type 1)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)
Ptpn1  (protein tyrosine phosphatase, non-receptor type 1)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)
PTPN1  (protein tyrosine phosphatase non-receptor type 1)


Additional Information