Characterization of novel VEGF (vascular endothelial growth factor)-C splicing isoforms from mouse

VEGF (vascular endothelial growth factor)-C is a major growth factor implicated in various physiological processes, such as angiogenesis and lymphangiogenesis. In the present paper, we report the identification of three short VEGF-C splicing isoforms (VEGF-C₆₂, VEGF-C₁₂₉ and VEGF-C₁₈₄) from immortalized mouse kidney PTECs (proximal tubular epithelial cells). Semi-quantitative RT (reverse transcription)-PCR analysis showed these isoforms were universally expressed to varying degrees in different tissues with high expression levels in the kidney. In immortalized PTECs and podocytes, VEGF-C₆₂ can activate phosphorylation of FAK (focal adhesion kinase) and promote cell adhesion to substratum. Cell survival was also increased by VEGF-C₆₂ treatment in the absence of serum. VEGF-C ₆₂ can also reduce cell proliferation in PTECs and podocytes. Nucleolin was one of the proteins that associated with VEGF-C₆₂ in pull-down assays using GST (glutathione transferase) fusion proteins as bait, indicating different protein binding requirements for VEGF-C₆₂ compared with VEGF-C. In conclusion, these newly identified VEGF-C isoforms represent a new class of proteins, which are potentially involved in epithelial cell adhesion and proliferation through novel receptor pathways.