Abstract
Vascular endothelial growth factor (VEGF) is both a growth factor and permeability factor, involved in tissue repair and as such, has been proposed to have a role in the pathogenesis of pulmonary fibrosis. VEGF is generated as multiple isoforms of two families, VEGFxxx and VEGFxxxb and mediates its effects through specific receptors, VEGFR-1 and VEGFR-2 and co-receptors, neuropilin-1 and neuropilin-2. We hypothesised that these receptors, co-receptors and isoforms would be differentially expressed in normal versus fibrotic fibroblasts.
Normal fibroblasts (NF) and fibrotic fibroblasts (FF) (from patients with proven UIP) were extracted from lung samples using the explant method. Expression of VEGFR-1, 2 and NRP1-1, NRP2 and VEGF isoforms was established at the protein level using western blotting whilst receptor expression was confirmed with immunofluorescence staining of cells in culture.
Both NF and FF expressed VEGFR1 and 2, NRP-1 and 2 and VEGFxxx/xxxb isoforms. No significant differences in VEGFR-2 and NRP-1 expression between NF and FF fibroblast were detected, however both VEGFR-1 and NRP-2 were significantly reduced in FF versus NF (p<0.05, non-paired t-test).
VEGF receptors, co-receptors and isoforms are expressed differentially in NF and FF. This suggests a potential role for changes in VEGF bioactivity in the development of pulmonary fibrosis.
- © 2012 ERS
