| Title: |
Vascular endothelial growth factor-C, a potential paracrine regulator of glomerular permeability, increases glomerular endothelial cell monolayer integrity and intracellular calcium |
| Authors: |
Foster, RR; Slater, SC; Seckley, J; Kerjaschki, D; Bates, DO; Mathieson, PW; Satchell, SC |
| Publication Year: |
2008 |
| Collection: |
University of Hong Kong: HKU Scholars Hub |
| Description: |
We have previously reported expression of vascular endothelial growth factor (VEGF)-A and -C in glomerular podocytes and actions of VEGF-A on glomerular endothelial cells (GEnC) that express VEGF receptor-2 (VEGFR-2). Here we define VEGFR-3 expression in GEnC and investigate the effects of the ligand VEGF-C. Renal cortex and cultured GEnC were examined by microscopy, and both cell and glomerular lysates were assessed by Western blotting. VEGF-C effects on trans-endothelial electrical resistance and albumin flux across GEnC monolayers were measured. The effects of VEGF-C156S, a VEGFR-3-specific agonist, and VEGF-A were also studied. VEGF-C effects on intracellular calcium ([Ca 2+]i) were measured using a fluorescence technique, receptor phosphorylation was examined by immunoprecipitation assays, and phosphorylation of myosin light chain-2 and VE-cadherin was assessed by blotting with phospho-specific antibodies. GEnC expressed VEGFR-3 in tissue sections and culture, and VEGF-C increased trans-endothelial electrical resistance in a dose-dependent manner with a maximal effect at 120 minutes of 6.8 Ω whereas VEGF-C156S had no effect. VEGF-C reduced labeled albumin flux by 32.8%. VEGF-C and VEGF-A increased [Ca2+]i by 15% and 39%, respectively. VEGF-C phosphorylated VEGFR-2 but not VEGFR-3, myosin light chain-2, or VE-cadherin. VEGF-C increased GEnC monolayer integrity and increased [Ca2+]i, which may be related to VEGF-C-S particular receptor binding and phosphorylation induction characteristics. These observations suggest that podocytes direct GEnC behavior through both VEGF-C and VEGF-A. Copyright © American Society for Investigative Pathology. ; link_to_subscribed_fulltext |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
American Journal of Pathology; 948; WOS:000259648000004; 938; https://hub.hku.hk/handle/10722/195463; 173 |
| DOI: |
10.2353/ajpath.2008.070416 |
| Availability: |
https://hub.hku.hk/handle/10722/195463; https://doi.org/10.2353/ajpath.2008.070416 |
| Accession Number: |
edsbas.B72AD26D |
| Database: |
BASE |