Experimental Study On Transduction Of Vascular Endothelial Growth Factor 165 Gene For Treating Scleroderma

Objective: Scleroderma is a kind of connective tissue disease characterized by fibrosis in multiple organs including skin. The microvascular modification is pathologic base of most clinical manifestation and complication of scleroderma. The vascular endothelial growth factor (VEGF) is a kind of multi-functional cytokine that specifically targets endothelial cells. VEGF can induce angiogenesis directly or indirectly. In view of the microvascular involvement in the pathogenesis of scleroderma, we hypothesize that angiogenesis in sclerotic skin induced by exogenous VEGF may improve skin sclerosis in scleroderma.Methods: A mouse model for scleroderma was establised by repeated local subcutaneous injections of bleomycin in mice. PhVEGF165 gene was transferred into the sclerotic skin of mouse by electroporatic technique. VEGF expression, angiogenesis and collagen synthesis in the sclerotic skin after PhVEGF165 gene transduction were examined by immunohistochemistry and in situ hybridization.Results: PhVEGF165 gene could be transferred into the mouse skin with electroporatic technique. VEGF gene expression was upregulated in the sclerotic skin after the gene transduction. The sclerotic condition of skin in the mouse model was improved with increased VEGF expression, angiogenesis and amelioration of atrophied dermis. Meanwhile, hair growth, regeneration of hair follicles and remarkably increased expression of collagen typeâ… mRNA in the sclerotic skin of the mouse model for scleroderma were also found.Conclusions: PhVEGF165 gene transduction could richen microvasculature in sclerotic skin and thicken the atrophied dermis in the mouse model for scleroderma. However, the dermal fibrosis in the sclerotic skin could not be relieved due to increased collagen...