Vascular endothelial growth factor-C accelerates diabetic wound healing.
Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing, whereas the importance of lymphangiogenesis for wound healing is unclear. We have examined whether overexpression of vascular endothelial growth factor (VEGF)-C via an adenoviral vector could improve the healing of full-thickness punch biopsy wounds in genetically diabetic (db/db) mice. We found that VEGF-C enhanced angiogenesis and lymphangiogenesis in the wound and significantly accelerated wound healing in comparison to the control wounds. VEGF-C also recruited inflammatory cells, some of which expressed VEGFR-3. On the other hand, when the function of endogenous VEGF-C/VEGF-D was blocked with a specific inhibitor, wound closure was delayed even further. These results suggest a function for VEGF-C in wound healing and demonstrate the therapeutic potential of VEGF-C in the treatment of diabetic wounds.
Saaristo
Anne
A
Molecular/Cancer Biology Laboratory, Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Hospital, Finland.
Tammela
Tuomas
T
Farkkilā
Anniina
A
Kärkkäinen
Marika
M
Suominen
Erkki
E
Yla-Herttuala
Seppo
S
Alitalo
Kari
K
D000818:Animals; D048909:Diabetes Complications / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics; D014947:Wounds and Injuries / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy
D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3