VEGF-C promotes survival in podocytes

Area of Science:

• Molecular Biology
• Cell Biology
• Renal Physiology

Background:

• Vascular Endothelial Growth Factor (VEGF)-A is a known autocrine survival factor for podocytes.
• Podocytes express VEGF receptors, including VEGF-R1 and VEGF-R3.
• VEGF-A is not a known ligand for VEGF-R3, prompting investigation into other VEGF family members.

Purpose of the Study:

• To examine the function of VEGF-C, a known VEGF-R3 ligand, in podocyte biology.
• To determine if VEGF-C's effects on podocytes are dependent on VEGF-R3.
• To elucidate the signaling pathways involved in VEGF-C-mediated podocyte survival.

Main Methods:

• Localization of VEGF-C and VEGF-D protein expression in podocytes and parietal epithelial cells.
• Intracellular calcium ([Ca2+]i) and cytotoxicity assays in human conditionally immortalized podocytes (hCIPs).
• Inhibition studies using VEGF-R3 kinase inhibitor (MAZ51) and tyrosine kinase inhibitor (SU-5416).
• Analysis of MAPK and Akt phosphorylation, and immunoprecipitation for VEGF-R3 autophosphorylation.

Main Results:

• VEGF-C protein is localized to podocytes.
• VEGF-C reduced intracellular calcium and cytotoxicity in hCIPs, similar to VEGF-A.
• VEGF-R3 inhibition (MAZ51) blocked VEGF-C's protective effect on cytotoxicity.
• VEGF-C reduced MAPK phosphorylation but not Akt phosphorylation.
• No VEGF-C-induced VEGF-R3 autophosphorylation was detected in hCIPs, but was observed in HMVECs.
• SU-5416, at concentrations specific for VEGF-R1, blocked VEGF-C's protective effect.

Conclusions:

• VEGF-C acts in an autocrine manner in cultured podocytes to promote cell survival.
• The study suggests a novel survival pathway for podocytes involving VEGF-C.
• The specific receptor or receptor complex activated by VEGF-C in podocytes remains to be elucidated.