Immunohistochemical analysis of vascular endothelial growth factor and hepatocyte growth factor, and their receptors, in transplanted islets in rats.
OBJECTIVE
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.
Watanabe
Hiroaki
H
Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
Sumi
Shoichiro
S
Kitamura
Yoshinori
Y
Nio
Yoshinori
Y
Higami
Tetsuya
T
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D007150:Immunohistochemistry; D016381:Islets of Langerhans Transplantation; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis*; D051381:Rats; D011917:Rats, Inbred Lew; D017978:Receptors, Growth Factor / Q000032:analysis; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor