Plgf 1

All GFs and chemokines were purchased in their mature forms, highly pure (>95% pure), carrier-free, and lyophilized^{35 (link)}. VEGF-A121, VEGF-A165, PlGF-1, PlGF-2, PDGF-AA, PDGF-BB, PDGF-CC, PDGF-DD, FGF-1, FGF-2, FGF-6, FGF-7, FGF-9, FGF-10, FGF-18, BMP-2, BMP-3, BMP-4, BMP-7, β-NGF, NT-3, BDNF, IGF-1, IGF-2, HB-EGF, CXCL-11, and CXCL-12α were purchased from PeproTech. CXCL-12γ was purchased from R&D systems. Except for PDGF-DD and BMP-7, which were produced in eukaryotic cells, all GFs were produced in Escherichia coli and thus were not glycosylated. All GFs were reconstituted and stored according to the provider’s instructions to regain full activity and prevent loss of protein.

Cell culture media RPMI 1640 Medium GlutaMAX^TM was obtained from Life Technologies. Human VEGF-A and PlGF-1 were from Peprotech. H₂DFFDA and CellROX were from Life Technologies. Hydrogen peroxide, methylglyoxal, NAC and 2-NBDG were from Sigma Aldrich. All the primers for qPCR were custom synthesised from Sigma Aldrich. Primer sequences are described in Supplementary Table S3.

Growth factors and inhibitors were used throughout the study in the concentrations indicated. Hepatocyte growth factor (HGF): 20 ng/ml (100-39), epidermal growth factor (EGF): 30 ng/ml (100-47), Insulin like Growth Factor 1 (IGF): 20 ng/ml (100-11), Netrin: 200 ng/ml (R&D Systems, 6419-N1-025), Platelet Derived Growth Factor-B (PDGF-B): 20 ng/ml (P100-14B), Tumour Necrosis Factor-α (TNF- α): 25 ng/ml (300-01A), basic Fibroblast Growth Factor (bFGF): 100 ng/ml (100-18B), Interleukin-6 (IL-6): 20 ng/ml (200-06), Nerve Growth Factor-β (NGF): 50 ng/ml (450-01), Transforming Growth Factor-β (TGF-β): 20 ng/ml (100-21) and Placental Growth Factor-1 (PlGF-1): 10 ng/ml (100-06) from PeproTech (London, UK), PHA-665752, 125 nM (Selleckchem, Houston, TX, USA, S1070), ARQ197, 125 nM (Active Biochemicals, Wanchai, Honkong, A-1109).