DIFFERENTIAL EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VASCULAR-PERMEABILITY FACTOR) FORMS IN RAT-TISSUES

Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), exists as multiple forms due to alternative splicing of mRNA. VEGF (165/164) (human/rodent homologue) is often assumed to be the predominant form, although truly quantitative assessments are lacking. We have used the RNase protection assay to directly quantitate the relative abundance of VEGF mRNA forms in five rat tissues (brain, kidney, lung, spleen, and heart) and two rat glioma cell lines (C6 and 9L). The three major forms, which code for proteins of 188, 164, and 120 amino acids, were observed in all of the tissues and cells examined. However, the relative abundance differed among the samples. VEGF(188) was the predominant form (>50% of total VEGF mRNA) in heart and lung, but was the least abundant form (6-15%) in all other samples. VEGF(164) was lower (similar to 25%) in heart and lung, but was predominant (>50%) in brain and kidney. VEGF(164) and VEGF(120) were present in equimolar amounts (each form similar to 46% of total) in the spleen, C6, and 9L. VEGF(120) was also present in kidney (38%) and lung (27%) and was least abundant (similar to 15%) in brain and heart. A rat homologue of VEGF(206) was not observed. VEGF mRNA splicing occurs in a tissue-specific manner. The assumption that the predominant physiologic form of VEGF is a VEGF (165/164) homodimer should be viewed with caution.