TAILIEUCHUNG - Báo cáo sinh học: "Combined vascular endothelial growth factor-A and fibroblast growth factor 4 gene transfer improves wound healing in diabetic mice"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Combined vascular endothelial growth factor-A and fibroblast growth factor 4 gene transfer improves wound healing in diabetic mice | Jazwa et al. Genetic Vaccines and Therapy 2010 8 6 http content 8 1 6 GENETIC VACCINES AND THERAPY RESEARCH Open Access Combined vascular endothelial growth factor-A and fibroblast growth factor 4 gene transfer improves wound healing in diabetic mice 1 111 1 Agnieszka Jazwa Paulina Kucharzewska Justyna Leja Anna Zagorska Aleksandra Sierpniowska Jacek Stepniewski1 Magdalena Kozakowska1 Hevidar Taha1 Takahiro Ochiya2 Rafal Derlacz3 Elisa Vahakangas4 Seppo Yla-Herttuala4 Alicja Jozkowicz1 Jozef Dulak1 Abstract Background Impaired wound healing in diabetes is related to decreased production of growth factors. Hence gene therapy is considered as promising treatment modality. So far efforts concentrated on single gene therapy with particular emphasis on vascular endothelial growth factor-A VEGF-A . However as multiple proteins are involved in this process it is rational to test new approaches. Therefore the aim of this study was to investigate whether single AAV vector-mediated simultaneous transfer of VEGF-A and fibroblast growth factor 4 FGF4 coding sequences will improve the wound healing over the effect of VEGF-A in diabetic db db mice. Methods Leptin receptor-deficient db db mice were randomized to receive intradermal injections of PBS or AAVs carrying p-galactosidase gene AAV-LacZ VEGF-A AAV-VEGF-A FGF-4 AAV-FGF4-IRES-GFP or both therapeutic genes AAV-FGF4-IRES-VEGF-A . Wound healing kinetics was analyzed until day 21 when all animals were sacrificed for biochemical and histological examination. Results Complete wound closure in animals treated with AAV-VEGF-A was achieved earlier day 19 than in control mice or animals injected with AAV harboring FGF4 both on day 21 . However the fastest healing was observed in mice injected with bicistronic AAV-FGF4-IRES-VEGF-A vector day 17 . This was paralleled by significantly increased granulation tissue formation vascularity and dermal matrix deposition. Mechanistically as shown in vitro FGF4 stimulated .

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