VEGF-C promotes survival in podocytes

RR Foster, SC Satchell, J Seckley, MS Emmett, KD Joory, CY Xing, MA Saleem, PW Mathieson, DO Bates, SJ Harper

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)


Vascular endothelial growth factor (VEGF)-A is an autocrine survival factor for podocytes, which express two VEGF receptors, VEGF-R1 and VEGF-R3. As VEGF-A is not a known ligand for VEGF-R3, the aim of this investigation was to examine whether VEGF-C, a known ligand for VEGF-R3, served a function in podocyte biology and whether this was VEGF-R3 dependent. VEGF-C protein expression was localized to podocytes in contrast to VEGF-D, which was expressed in parietal epithelial cells. Intracellular calcium ([Ca2+]i) experiments demonstrated that VEGF-C induced a 0.74 {+/-} 0.09-fold reduction in [Ca2+]i compared with baseline in human conditionally immortalized podocytes (hCIPs; P <0.05, one sample t-test, n = 8). Cytotoxicity experiments revealed that in hCIPs VEGF-C reduced cytotoxicity to 81.4 {+/-} 1.9% of serum-starved conditions (P <0.001, paired t-test, n = 16), similar to VEGF-A (82.8 {+/-} 4.5% of serum-starved conditions, P <0.05, paired t-test). MAZ51 (a VEGF-R3 kinase inhibitor) inhibited the VEGF-C-induced reduction in cytotoxicity (106.2 {+/-} 2.1% of serum-starved conditions), whereas MAZ51 by itself had no cytotoxic effects on hCIPs. VEGF-C was also shown to induce a 0.5 {+/-} 0.13-fold reduction in levels of MAPK phosphorylation compared with VEGF-A and VEGF-A-Mab treatment (P <0.05, ANOVA, n = 4), yet had no effect on Akt phosphorylation. Surprisingly, immunoprecipitation studies detected no VEGF-C-induced autophosphorylation of VEGF-R3 in hCIPs but did so in HMVECs. Moreover, SU-5416, a tyrosine kinase inhibitor, blocked the VEGF-C-induced reduction in cytotoxicity (106 {+/-} 2.8% of serum-starved conditions) at concentrations specific for VEGF-R1. Together, these results suggest for the first time that VEGF-C acts in an autocrine manner in cultured podocytes to promote survival, although the receptor or receptor complex activated has yet to be elucidated.
Translated title of the contributionVEGF-C promotes survival in podocytes
Original languageEnglish
Pages (from-to)F196 - F207
Number of pages12
JournalAJP - Renal Physiology
Volume291 (1)
Publication statusPublished - Jul 2006

Bibliographical note

Publisher: American Physiological Society

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