Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice (Articolo in rivista)

Type
Label
  • Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1007/s00125-004-1414-7 (literal)
Alternative label
  • Graiani G.1; Emanueli C.2; Desortes E.2; Van Linthout S.2; Pinna A.2; Figueroa C.D.3; Manni L.4; Madeddu P.2,5 (2004)
    Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice
    in Diabetologia (Berl.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Graiani G.1; Emanueli C.2; Desortes E.2; Van Linthout S.2; Pinna A.2; Figueroa C.D.3; Manni L.4; Madeddu P.2,5 (literal)
Pagina inizio
  • 1047 (literal)
Pagina fine
  • 1054 (literal)
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  • 47 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 6 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1 Department of Pathology, University of Parma, Italy; 2 Experimental Medicine and Gene Therapy Section, National Institute of Biostructures and Biosystems (INBB), 07033, Osilo (Sassari), Italy; 3 Department of Pathology, Austral Universidad, Valdivia, Chile; 4 Institute for Cardiovascular Research, Wallenberg Laboratory, Sahlgrenska University Hospital/Sahlgrenska, Göteborg, Sweden; 5 Internal Medicine, University of Sassari, Italy (literal)
Titolo
  • Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice (literal)
Abstract
  • AIMS/HYPOTHESIS: The neurotrophin nerve growth factor (NGF) is pro-angiogenic and facilitates wound repair. The present study was conducted to (i) assess the statement of NGF system components in diabetic wounds and (ii) evaluate whether NGF supplementation could prevent impairment of wound neoangiogenesis by diabetes. METHODS: Skin wounds were produced in the interscapular region of streptozotocin-induced diabetic mice. NGF (1 microg per day in PBS) or vehicle was applied onto the ulcers for 3 days after punching. Non-diabetic mice were used as controls. RESULTS: In wounds of untreated diabetic mice, endogenous levels of immunoreactive NGF were lower than those in wounds of non-diabetic mice ( p<0.01). Immunohistochemical analysis showed down-regulation of tyrosine kinase receptor-A (TrkA) and up-regulation of p75 receptor in granulation tissue microvasculature. Local NFG administration prevented diabetes-induced expressional alterations, enhanced reparative capillarisation ( p<0.01), and accelerated wound closure ( p<0.01). This was associated with a three-fold increase in endothelial cell proliferation ( p<0.01), while apoptosis was reduced by 50% ( p<0.05). Quantitative RT-PCR documented a 5.5-fold increase in the expression of vascular endothelial growth factor-A (VEGF-A) by exogenous NGF in diabetic tissues ( p<0.01). In in vitro preparations of human endothelial cells from derma, NGF increased the release of immunoreactive VEGF-A, and reduced high-glucose-induced apoptosis ( p<0.05), the latter effect being inhibited by a VEGF-A receptor-2 antagonist. CONCLUSIONS/INTERPRETATION: Diabetic ulcers display distinct alterations in reparative angiogenesis and in the expression of NGF and its receptors. NGF supplementation corrects endogenous liabilities, facilitates vascular regeneration, and suppresses endothelial apoptosis seemingly via VEGF-A. Our findings unravel new mechanisms responsible for NGF reparative action. (literal)
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