Immunohistochemical analysis of vascular endothelial growth factor and hepatocyte growth factor, and their receptors, in transplanted islets in rats.
PURPOSE: Our previous studies showed that transplanted islets increasingly express a marker of neovascularization, platelet endothelial cell adhesion molecule-1 (PECAM-1), as well as vascular endothelial growth factor (VEGF). Hepatocyte growth factor (HGF) is another stimulator of neovascularization. In this study, we examined the expression of these growth factors and their receptors; fetal liver kinase-1 (Flk-1) for VEGF and c-Met for HGF, to acertain whether VEGF and HGF play a role in the neovascularization of transplanted islets. METHODS: Islets were isolated from male Lewis rats by collagenase digestion and the discontinuous dextran gradient method, then transplanted into the bilateral subnephrocapsular space. The kidneys were excised 1-28 days after transplantation, then fixed in formaldehyde and embedded in paraffin. Serial slices were immunostained for VEGF, HGF, Flk-1, or c-Met, respectively. RESULTS: Islets in the normal pancreas were positively stained for VEGF, HGF, and c-Met; however, Flk-1 was only stained at the periphery of the islets. In the transplanted islets, staining for VEGF, HGF, and c-Met was positive, but Flk-1 was not stained. Moreover, staining for HGF and c-Met became stronger in the transplanted islets with time. CONCLUSIONS: These results suggest that HGF, rather than VEGF, may play a role in the neovascularization of transplanted islets.[1]References
- Immunohistochemical analysis of vascular endothelial growth factor and hepatocyte growth factor, and their receptors, in transplanted islets in rats. Watanabe, H., Sumi, S., Kitamura, Y., Nio, Y., Higami, T. Surgery today. (2003) [Pubmed]
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