File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: VEGF-C promotes survival in podocytes

TitleVEGF-C promotes survival in podocytes
Authors
Issue Date2006
Citation
American Journal of Physiology - Renal Physiology, 2006, v. 291 n. 1, p. F196-F207 How to Cite?
AbstractVascular 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. Copyright © 2006 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/195437
ISSN
2008 Impact Factor: 3.89
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFoster, RR-
dc.contributor.authorSatchell, SC-
dc.contributor.authorSeckley, J-
dc.contributor.authorEmmett, MS-
dc.contributor.authorJoory, K-
dc.contributor.authorXing, CY-
dc.contributor.authorSaleem, MA-
dc.contributor.authorMathieson, PW-
dc.contributor.authorBates, DO-
dc.contributor.authorHarper, SJ-
dc.date.accessioned2014-02-28T06:12:09Z-
dc.date.available2014-02-28T06:12:09Z-
dc.date.issued2006-
dc.identifier.citationAmerican Journal of Physiology - Renal Physiology, 2006, v. 291 n. 1, p. F196-F207-
dc.identifier.issn0363-6127-
dc.identifier.urihttp://hdl.handle.net/10722/195437-
dc.description.abstractVascular 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. Copyright © 2006 the American Physiological Society.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Physiology - Renal Physiology-
dc.titleVEGF-C promotes survival in podocytes-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajprenal.00431.2005-
dc.identifier.pmid16525158-
dc.identifier.scopuseid_2-s2.0-33745431660-
dc.identifier.volume291-
dc.identifier.issue1-
dc.identifier.spageF196-
dc.identifier.epageF207-
dc.identifier.isiWOS:000238121900021-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats