Differential Expression of Vascular Endothelial Growth Factor (Vascular Permeabilty Factor) Forms in Rat Tissues

Abstract

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. VEGF₁₈₈ 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. VEGF₁₆₄ was lower (∼25%) in heart and lung, but was predominant (>50%) in brain and kidney. VEGF₁₆₄ and VEGF₁₂₀ were present in equimolar amounts (each form ∼46% of total) in the spleen, C6, and 9L. VEGF₁₂₀, was also present in kidney (38%) and lung (27%) and was least abundant (∼15%) in brain and heart. A rat homologue of VEGF₂₀₆ 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.

Key Words:

• VEGF
• VPF
• vasculature
• angiogenesis